University of Wisconsin Hematology

Thrombocytopenic disorders

General

  1. Kaushansky K. Thrombopoietin. NEJM 1998;339:746
  2. Kaushansky K. Historical review: megakaryopoiesis and thrombopoiesis. Blood 2008;111:981
  3. Izzi et al. Learning by counting blood platelets in population studies: survey and perspective a long way after Bizzozero. J Thromb Haemost 2018;16:1711 (Review of genetic and non-genetic determinants of the platelet count, health implications of variations in the count)
  4. Cines et al.  Congenital and acquired thrombocytopenia.  Hematology 2004:390
  5. Eto and Kunishima. Linkage between the mechanisms of thrombocytopenia and thrombopoiesis. Blood 2016;127:1234
  6. Warkentin T. Drug-induced immune-mediated thrombocytopenia – from purpura to thrombosis. (Editorial) NEJM 2007;356:891
  7. Biino et al. Influence of age, sex and ethnicity on platelet count in five Italian geographic isolates: mild thrombocytopenia may be physiological. Br JHaematol 2012;157:384
  8. Han et al. Why thromboembolism occurs in some patients with thrombocytopenia and treatment strategies. Thromb Res 2020;196:500
  9. Foy et al. How I diagnose and treat thrombocytopenia in geriatric patients. Blood 2024;143:214

Inherited thrombocytopenias

  1. Warren and Di Paola. Genetics of inherited thrombocytopenias. Blood 20200;139:3264
  2. Bianchi et al. Genomic landscape of megakaryopoiesis and platelet function defects. Blood 2016;127:1249
  3. Songdej and Rao. Hematopoietic transcription factor mutations: important players in inherited platelet defects. Blood 2017;129:2873
  4. Favier and Raslova. Progress in understanding the diagnosis and molecular genetics of macrothrombocytopenias. Br J Haematol 2015;170:626
  5. Drachman J. Inherited thrombocytopenia: when a low platelet count does not mean ITP. Blood 2004;103:390
  6. Balduni et al. Inherited thrombocytopenias frequently diagnosed in adults. J Thromb Haemost 2013;11:1006
  7. Imai et al.  Clinical course of patients with WASP gene mutations. Blood 2004;103:456. (Wiskott-Aldrich syndrome)
  8. Bosticardo et al. Recent advances in understanding the pathophysiology of Wiskott-Aldrich syndrome. Blood 2009;113:6288
  9. Burns et al.  Mechanisms of WASp-mediated hematologic and immunologic disease. Blood 2004;104:3454  (Wiskott-Aldrich syndrome)
  10. Albert et al. X-linked thrombocytopenia (XLT) due to WAS mutations: clinical characteristics, long-term outcome, and treatment optiions. Blood 2010;115:3231
  11. Vallée et al. Wiskott-Aldrich syndrome: a study of 577 patients defines the genotype as a biomarker for disease severity and survival. Blood 2024;143:2504
  12. Lopez et al. Bernard-Soulier syndrome. Blood 1998;91:4397
  13. Sivapalaratnam et al. Rare variants in GP1BB are responsible for autosomal dominant macrothrombocytopenia. Blood 2017;129:520
  14. Marín-Quílez et al. Novel variants in GALE cause syndromic macrothrombocytopenia by disrupting glycosylation and thrombopoiesis. Blood 2023;141:406
  15. Noris et al. Platelet diameters in inherited thrombocytopenias: analysis of 376 patients with all known disorders. Blood 2014;124 (6):e4
  16. Manchev et al. A new form of macrothrombocytopenia induced by a germ-line mutation in the PRKACG gene. Blood 2014;124:2554(Severe thrombocytopenia with bleeding, recessive inheritance)
  17. Bottega et al. ACTN1-related thrombocytopenia: identification of novel families for phenotypic characterization. Blood 2015;125:869(A relatively common, dominantly inherited form of mild macrothrombocytopenial; mutation in α-actinin1 gene)
  18. Bastida et al. Two novel variants of the ABCG5 gene cause xanthelasmas and macrothrombocytopenia: a brief review of hematologic abnormalities of sitosterolemia. J Thromb Haemost 2017;9:1859(Macrothrombocytopenia, stomatocytosis)
  19. Lentaigne et al. Germline mutations in the transcription factor IKZF5 cause thrombocytopenia. Blood 2019;134:2070 (Dominant inheritance, decr alpha granules)
  20. Pecci et al. Position of nonmuscle myosin heavy chain IIA (NMMHC‐IIA) mutations predicts the natural history of MYH9‐related disease. Hum Mutat 2008;29:409
  21. Pecci et al. Eltrombopag for the treatment of the inherited thrombocytopenia deriving from MYH9 mutations. Blood 2010;116:5832(11/12 patients responded)
  22. Gerrits et al. Effects of eltrombopag on platelet count and platelet activation in Wiskott-Aldrich syndrome/X-linked thrombocytopenia. Blood 2015;126:1367
  23. Zaninetti et al. Extramedullary hematopoiesis: a new feature of inherited thrombocytopenias? J Thromb Haemost 2017;15:2226
  24. Shinawi et al. Syndromic thrombocytopenia and predisposition to acute myelogenous leukemia caused by constitutional microdeletions on chromosome 21q. Blood 2008;112:1042
  25. Homan et al. Hereditary platelet disorders associated with germ line variants in RUNX1, ETV6, and ANKRD26. Blood 2023;141:1533
  26. Simon et al. High frequency of germline RUNX1 mutations in patients with RUNX1-mutated AML. Blood 2020;135:1882
  27. Cunningham et al. Natural history study of patients with familial platelet disorder with associated myeloid malignancy. Blood 2023;142:2146 (RUNX1)
  28. Wahlster et al. ANKRD26-related thrombocytopenia 2 with a baseline increase in blasts: implications for clinical surveillance. Blood 2025;146:254 (Increased marrow blasts without progression to myeloid malignancy)

ITP

  1. Cooper and Ghanima. Immune thrombocytopenia. NEJM 2019;381:945
  2. Lambert and Gernsheimer. Clinical updates in adult immune thrombocytopenia. Blood 2017;129:2829
  3. Neunert et al. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood 2011;117:4190
  4. Al-Samkari et al. A modern reassessment of glycoprotein-specific direct platelet autoantibody testing in immune thrombocytopenia. Blood Adv 2020;4:9
  5. Schmidt et al. Anti‐platelet antibodies in childhood immune thrombocytopenia: Prevalence and prognostic implications, J Thromb Haemost 2020;18:1210
  6. Taparia et al. Frequency and utility of bone marrow examination in relapsed/refractory immune thrombocytopenia. J Thromb Haemost 2022;20:2119 (Only 2% of biopsies had abnormal findings)
  7. Neunert C. Current management of immune thrombocytopenia. Hematology 2013:276
  8. Provan et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood 2010;115:168
  9. Liebman and Pullarkat. Diagnosis and management of immune thrombocytopenia in the era of thrombopoietin mimetics. Hematology 2011:384
  10. Cines et al. The ITP syndrome: pathogenic and clinical diversity. Blood 2009;113:6511
  11. Moulis et al. Epidemiology of incident immune thrombocytopenia: a nationwide population-based study in France. Blood 2014;124:3308(Incidence 2.9/100K/yr; severe bleeding rare but more common in older people)
  12. Arnold et al. Misdiagnosis of primary immune thrombocytopenia and frequency of bleeding: lessons from the McMaster ITP Registry. Blood Adv 2017;1:2414
  13. Heitink-Pollé et al. Clinical and laboratory predictors of chronic immune thrombocytopenia in children: a systematic review and meta-analysis. Blood 2014;124:3295(Older age, insidious onset, no preceding infection, mild bleeding, and higher platelet count predict chronic ITP; IVIG may protect against it)
  14. Webert et al.  A retrospective 11-year analysis of obstetric patients with idiopathic thrombocytopenic purpura. Blood 2003;102:4306
  15. Lostau et al. Effect of pregnancy on the course of immune thrombocytopenia: a retrospective study of 118 pregnancies in 82 women. Br J Haematol 2014;166:929
  16. Grimaldi-Bensouda et al. A case-control study to assess the risk of immune thrombocytopenia associated with vaccines. Blood 2012;120:4938 (Exposure to vaccines not associated with development of ITP in adults)
  17. Moulis et al.  De novo and relapsed immune thrombocytopenia after COVID-19 vaccines: results of French safety monitoring. Blood 2022;139:2561  (Incidence less than 2 cases per million)
  18. Quach et al. Fc-independent immune thrombocytopenia via mechanomolecular signaling in platelets. Blood 2018;131:787(Antibodies against the ligand-binding domain of GP1b cause Fc receptor-independent platelet clearance, may cause steroid and IVIG resistance. With editorial)
  19. Morodomi et al. Mechanisms of anti-GPIbα antibody–induced thrombocytopenia in mice. Blood 2020;135:2292(anti-GP1b antibodies cause megakaryocytes to produce platelets with low GP1b expression)
  20. Malik et al. The role of CD8+ T-cell clones in immune thrombocytopenia. Blood 2023;141:2417 (Antibody-independent platelet destruction in chronic ITP)
  21. van Dijk et al. Evaluation of the procoagulant state in chronic immune thrombocytopenia before and after eltrombopag treatment—a prospective cohort study. J Thromb Haemost 2023;21:1020 (Evidence of hypercoagulability in untreated ITP)

Complications – bleeding and other

  1. Piel-Julian et al. Risk factors for bleeding, including platelet count threshold, in newly diagnosed immune thrombocytopenia adults. J Thromb Haemost 2018;16:1830(Bleeding threshold around 20K platelets; platelet count not a good predictor of severe bleeding, however)
  2. Cohen et al. The bleeding risk and natural history of idiopathic thrombocytopenic purpura in patients with persistent low platelet counts. Arch Intern Med 2000;160:1630(5 year mortality 2.2% for those under 40, 48% for those over 60)
  3. Neunert et al. Severe bleeding events in adults and children with primary immune thrombocytopenia: a systematic review. J Thromb Haemost 2015;13:457
  4. Neunert et al. Severe hemorrhage in children with newly diagnosed immune thrombocytopenic purpura. Blood 2008;112:4003(severe bleeding uncommon at diagnosis and rarely begins within 4 weeks after diagnosis)
  5. Psaila et al. Intracranial hemorrhage (ICH) in children with immune thrombocytopenia (ITP): study of 40 cases. Blood 2009;114:4777(0.19% to 0.78% incidence; children with severe thrombocytopenia plus head trauma or hematuria at greatest risk)
  6. Neunert et al. Bleeding manifestations and management of children with persistent and chronic immune thrombocytopenia: data from the Intercontinental Cooperative ITP Study Group (ICIS). Blood 2013;121:4457(“ITP is a benign condition for most affected children and that major hemorrhage, even with prolonged severe thrombocytopenia, is rare”)
  7. Cortelazzo et al. High risk of severe bleeding in aged patients with chronic idiopathic thrombocytopenic purpura. Blood 1991; 77:31
  8. Portieleje et al. Morbidity and mortality in adults with idiopathic thrombocytopenic purpura. Blood 2001;97:2549
  9. Nørgaard et al. Long-term clinical outcomes of patients with primary chronic immune thrombocytopenia: a Danish population-based cohort study. Blood 2011;117:3514
  10. Moulis et al. Infections in non-splenectomized persistent or chronic primary immune thrombocytopenia adults: risk factors and vaccination effect. J Thromb Haemost 2017;15:785(Lung dz, steroids and rituximab increase risk; pneumococcal and influenza vaccines beneficial)
  11. Hill and Newland. Fatigue in immune thrombocytopenia. Br J Haematol 2015;170:141
  12. Rizvi et al. United Kingdom immune thrombocytopenia registry: retrospective evaluation of bone marrow fibrosis in adult patients with primary immune thrombocytopenia and correlation with clinical findings. Br J Haematol 2015;169:590 (25% of TPO-RA naive patients had increased reticulin fibrosis in marrow)
  13. Ruggeri et al. Thrombotic risk in patients with primary immune thrombocytopenia is only mildly increased and explained by personal and treatment-related risk factors. J Thromb Haemost 2014;12:1266
  14. Chandan et al. The association between idiopathic thrombocytopenic purpura and cardiovascular disease: a retrospective cohort study. J Thromb Haemost 2018;16:474 (38% higher CV risk in ITP; risk increased after splenectomy)
  15. Balitsky et al. Managing antithrombotic therapy in immune thrombocytopenia: development of the TH2 risk assessment score. Blood 2018;132:2684
  16. Ollier et al. Platelet count threshold for hemorrhage in patients with immune thrombocytopenia treated with antiplatelet agents. NEJM 2023;142:1099 (Most bleeds in ASA-treated patients occurred with plts < 20K)
  17. Adelborg et al. Cardiovascular and bleeding outcomes in a population‐based cohort of patients with chronic immune thrombocytopenia. J Thromb Haemost 2019;17:912 (Risk of cardiovascular events not predicted by platelet count; bleeding rate higher whem platelets <50K)
  18. Mithoowani et al. Management of major bleeds in patients with immune thrombocytopenia. J Thromb Haemost 2020;18:1790
  19. Cooper et al. Identification of occult cerebral microbleeds in adults with immune thrombocytopenia. Blood 2020;136:2875(MRI found microbleeds in 43% of ITP patients, particularly when nadir plt count <10K)
  20. Guillet et al. Immune thrombocytopenia and pregnancy: an exposed/nonexposed cohort study. Blood 2023;141:11 (Risk of severe bleeding does not increase during pregnancy)

Treatment

  1. Cines and Bussel.  How I treat idiopathic thrombocytopenic purpura (ITP). Blood 2005;106:2244
  2. Bussel et al Management of Primary Immune Thrombocytopenia in Pregnancy. NEJM 2023;389:540
  3. Ghanima et al. How I treat immune thrombocytopenia: the choice between splenectomy or a medical therapy as a second-line treatment. Blood 2012;120:960
  4. Miltiadous et al. Identifying and treating refractory ITP: difficulty in diagnosis and role of combination treatment. Blood 2020;135:472
  5. Ghanima et al. How I treat primary ITP in adult patients who are unresponsive to or dependent on corticosteroid treatment. Blood 2021;137:2736
  6. Cuker and Neunert. How I treat refractory immune thrombocytopenia. Blood 2016;128:1547
  7. Mahévas et al. Characteristics, outcome, and response to therapy of multirefractory chronic immune thrombocytopenia. Blood 2016;128:1625(70% response rate to immunosuppression + TPO receptor agonist)
  8. Gernsheimer et al. Mechanisms of response to treatment in autoimmune thrombocytopenic purpura. NEJM 1989; 320:974
  9. Mazzucconi et al. Therapy with high-dose dexamethasone (HD-DXM) in previously untreated patients affected by idiopathic thrombocytopenic purpura: a GIMEMA experience. Blood 2007;109:1401
  10. Wei et al. High-dose dexamethasone vs prednisone for treatment of adult immune thrombocytopenia: a prospective multicenter randomized trial. Blood 2016;127:296(Initial response rates better with dex, sustained response rates similar; dex better tolerated)
  11. Zaja et al. Dexamethasone plus rituximab yields higher sustained response rates than dexamethasone monotherapy in adults with primary immune thrombocytopenia. Blood 2010;115:2755(63% vs 36% sustained response rate)
  12. Gudbrandsdottir et al. Rituximab and dexamethasone vs dexamethasone monotherapy in newly diagnosed patients with primary immune thrombocytopenia. Blood 2013;121:1976(R+D gave higher response rates, more durable remissions than D alone)
  13. Bradbury et al. Mycophenolate Mofetil for First-Line Treatment of Immune Thrombocytopenia. NEJM 2021;385:885(MMF improved response rates but decreased QOL; with editorial)
  14. Chaturvedi et al. Splenectomy for immune thrombocytopenia: down but not out. Blood 2018:131:1172
  15. Kojouri et al. Splenectomy for adult patients with idiopathic thrombocytopenic purpura: a systematic review to assess long-term platelet count responses, prediction of response, and surgical complications. Blood 2004;104:2623
  16. Boyle et al. Splenectomy and the incidence of venous thromboembolism and sepsis in patients with immune thrombocytopenia. Blood 2013;121:4782
  17. Vesely et al.  Management of Adult Patients with Persistent Idiopathic Thrombocytopenic Purpura Following Splenectomy. Ann Intern Med 2004;140:112
  18. Godeau et al. Treatment of adult chronic autoimmune thrombocytopenic purpura with repeated high-dose intravenous immunoglobulin. Blood 1993;82:1415
  19. Law et al. High-dose intravenous immune globulin and the response to splenectomy in patients with idiopathic thrombocytopenic purpura. NEJM 1997;336:1494
  20. Heitink-Pollé et al. Intravenous immunoglobulin vs observation in childhood immune thrombocytopenia: a randomized controlled trial. Blood 2018;132:883(Upfront IVIG associated with higher CR rates and less bleeding, but no decrease in relapse rate)
  21. Scaradavou et al. Intravenous anti-D treatment of immune thrombocytopenic purpura: experience in 272 patients. Blood 1997;89:2689
  22. Despotovic et al. RhIG for the treatment of immune thrombocytopenia: consensus and controversy. Transfusion 2011;52:1126
  23. Robak et al. Rozrolimupab, a mixture of 25 recombinant human monoclonal RhD antibodies, in the treatment of primary immune thrombocytopenia. Blood 2012;120:3670
  24. Cheng et al.  Initial tratment of immune thrombocytopenic purpura with high-dose dexamethasone.  NEJM 2003;349:831
  25. Figueroa et al. Combination chemotherapy in refractory immune thrombocytopenic purpura. N Engl J Med 1993;328:1226
  26. Boruchov et al. Multiagent induction and maintenance therapy for patients with refractory immune thrombocytopenic purpura (ITP). Blood 2007;110:3526(IVIG, steroids, vincristine, IV anti-D induction plus danazol, azathioprine maintenance)
  27. Arnold et al. Combination immunosuoppressant therapy for aptients with chronic refractory immune thrombocytopenic purpura. Blood 2010;115:29 (Mycophenolate, azathioprine and cyclosporine combination produced over 70% CR rate, median duration of CR 24 mo)
  28. Choi et al. A novel triple therapy for ITP using high-dose dexamethasone, low-dose rituximab, and cyclosporine (TT4). Blood 2015;126:500(60% 6-mo OR rate, little toxicity)
  29. Stasi et al. Rituximab chimeric anti-CD20 monoclonal antibody treatment for adults with chronic idiopathic thrombocytopenic purpura. Blood 2001;98:952
  30. McMillan and Durette. Long-term outcomes in adults with chronic ITP after splenectomy failure. Blood 2004;104:956
  31. Gómez-Almaguer et al. Low-dose rituximab and alemtuzumab combination therapy for patients with steroid-refractory autoimmune cytopenias. Blood 2010;116:4783
  32. Arnold et al. Systematic Review: Efficacy and Safety of Rituximab for Adults with Idiopathic Thrombocytopenic Purpura. Ann Intern Med 2007;146:25   (62.5% response rate, 2.9% death rate in uncontrolled trials)
  33. Godeau et al. Rituximab efficacy and safety in adult splenectomy candidates with chronic immune thrombocytopenic purpura: results of a prospective multicenter phase 2 study. Blood 2008;112:999 (40% had good response, over half avoided splenectomy)
  34. Stasi et al. Response to B-cell–depleting therapy with rituximab reverts the abnormalities of T-cell subsets in patients with idiopathic thrombocytopenic purpura. Blood 2007;110:2924
  35. Patel et al. Outcomes 5 years after response to rituximab therapy in children and adults with immune thrombocytopenia. Blood 2012;119:5989(21% of adults with initial CR to rituximab remained in remission without further treatment after 5 years; no significant toxicity observed)
  36. Mahévas et al. B cell depletion in ummune thrombocytopenia reveals splenic long-lived plasma cells. J Clin Invest 2013;123:432(Rituximab treatment may promote development of long-lived platelet-reactive plasma cells)
  37. Khellaf et al. Safety and efficacy of rituximab in adult immune thrombocytopenia: results from a prospective registry including 248 patients. Blood 2014;124:3228(61% initial response rate, 39% sustained responses, relatively low toxicity)
  38. Ghanima et al. Rituximab as second-line treatment for adult immune thrombocytopenia (the RITP trial): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet 2015;385:1653(Longer remission rate, lower splenectomy rate with rituximab vs placebo)
  39. Audia et al Preferential splenic CD8+ T-cell activation in rituximab-nonresponder patients with immune thrombocytopenia. Blood 2013;122:2477
  40. Nazi et al. The effect of rituximab on vaccine responses in patients with immune thrombocytopenia. Blood 2013;122:1946(Ab response to vaccination decreased for at least 6 mo after rituximab treatment)
  41. Bradbury et al. Mycophenolate Mofetil for First-Line Treatment of Immune Thrombocytopenia. NEJM 2021;385:885(Better response and lower risk of refractory or relapsed disease, but somewhat lower quality of life with MMF vs steroids; with editorial)
  42. Connell and Berliner. Fostamatinib for the treatment of chronic immune thrombocytopenia. Blood 2019;133:2027
  43. González-López et al. Fostamatinib effectiveness and safety for immune thrombocytopenia in clinical practice. Blood 2024;144:646
  44. Han et al. Low-dose decitabine modulates T-cell homeostasis and restores immune tolerance in immune thrombocytopenia. Blood 2021;138:674
  45. Rodrigo and Gooneratne. Dapsone for primary immune thrombocytopenia in adults and children: an evidence-based review. J Thromb Haemost 2013;11:1946
  46. Colella et al. A retrospective analysis of 122 immune thrombocytopenia patients treated with dapsone: Efficacy, safety and factors associated with treatment response. J Thromb Haemost 2021;19:2275(Efficacy may depend on drug’s ability to cause hemolysis)
  47. Feng et al. Oral all-trans retinoic acid plus danazol versus danazol as second-line treatment in adults with primary immune thrombocytopenia: a multicentre, randomised, open-label, phase 2 trial. Lancet Haematol 2017;4:e487(Adding ATRA to danazol increased response rate from 25% to 62% with little toxicity; with editorial)
  48. Wu et al. All-trans retinoic acid plus low-dose rituximab vs low-dose rituximab in corticosteroid-resistant or relapsed ITP. Blood 2022;139:333 (Response rate increased from 56% to 80% by adding ATRA)
  49. Kuter et al. Rilzabrutinib, an Oral BTK Inhibitor, in Immune Thrombocytopenia. NEJM 2022;386:1421 (“…rapid and durable clinical activity that improved with length of treatment”)
  50. Michel et al.  Does Helicobater pylori initiate or perpetuate immune thrombocytopenic purpura? Blood 2004;103:890  (It apparently did not in this series)
  51. Sato et al. Effect of Helicobacter pylori Eradication on Platelet Recovery in Patients With Chronic Idiopathic Thrombocytopenic Purpura.  Arch Intern Med 2004;164:1904
  52. Emilia et al. Helicobacter pylori infection and chronic immune thrombocytopenic purpura: long-term results of bacterium eradication and association with bacterium virulence profiles. Blood 2007;110:3833(51% of ITP patients had H pylori infection; 68% had improvement in ITP upon eradication of infection)
  53. Stasi et al. Effects of eradication of Helicobacter pylori infection in patients with immune thrombocytopenic purpura: a systematic review. Blood 2009; 113:1231 (about a third of patients improve after treatment for H pylori, but response rates vary widely in different countries)
  54. van den Berg et al. Daratumumab for immune thrombotic thrombocytopenic purpura. Blood Adv 2022;6:993
  55. Chen et al. A Novel Anti-CD38 Monoclonal Antibody for Treating Immune Thrombocytopenia. NEJM 2024;390:2178
  56. Sun et al. Daratumumab in Relapsed or Refractory Pediatric Immune Thrombocytopenia. NEJM 2025;392:2069
  57. Broome et al. Efficacy and safety of the neonatal Fc receptor inhibitor efgartigimod in adults with primary immune thrombocytopenia (ADVANCE IV): a multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 2023;402:1648

Thrombopoietic drugs in ITP and other thrombocytopenias

  1. Imbach and Crowther. Thrombopoietin-Receptor Agonists for Primary Immune Thrombocytopenia. NEJM 2011;365:734
  2. Bussel et al. AMG 531, a Thrombopoiesis-Stimulating Protein, for Chronic ITP. NEJM 2006;355:1672(Romiplostim)
  3. Kuter et al. Romiplostim or standard of care in patients with immune thrombocytopenia. NEJM 2010;363:1889(Romiplistim treatment associated with higher response rate, fewer complications, higher quality of life)
  4. Bussel et al. Safety and efficacy of long-term treatment with romiplostim in thrombocytopenic patients with chronic ITP. Blood 2009;113:2161
  5. Palandri et al. Real-world use of thrombopoietin receptor agonists in older patients with primary immune thrombocytopenia.Blood 2021;138:571(TRAs effective, use cautiously in pts with history of thrombosis)
  6. Khellaf et al. Romiplostim safety and efficacy for immune thrombocytopenia in clinical practice: 2-year results of 72 adults in a romiplostim compassionate-use program. Blood 2011;118:4338
  7. Newland et al. Remission and platelet responses with romiplostim in primary immune thrombocytopenia: final results from a phase 2 study. Br J Haematol 2016;172:262(About 30% of responding patients able to stop drug without recurrent severe thrombocytopenia)
  8. Guillet et al. Prolonged response after TPO-RA discontinuation in primary ITP: results of a prospective multicenter study. Blood 2023;141:2867 (About 30% of patients who had CR on treatment maintained plts > 30K 1 year after stopping treatment)
  9. Cottu et al. Long-term follow-up of the STOPAGO study. Blood 2025;145:244 (About half of patients who had CR after 1 year on TPO-RA maintained that response after 4 years off treatment; most relapses happen early)
  10. Kuter et al. Evaluation of bone marrow reticulin formation in chronic immune thrombocytopenia patients treated with romiplostim. Blood 2009;114:3748
  11. Ghanima et al. Bone marrow fibrosis in 66 patients with immune thrombocytopenia treated with thrombopoietin-receptor agonists: a single-center, long-term follow-up. Haematologica 2014;99:937(Grade 2 or 3 fibrosis found in about 20% of patients treated > 2 yrs)
  12. Kantarjian et al. Phase 2 study of romiplostim in patients with low- or intermediate-risk myelodysplastic syndrome receiving azacitidine therapy. Blood 2010;116:3163(Uncertain benefit)
  13. Bussel et al. Eltrombopag for the Treatment of Chronic Idiopathic Thrombocytopenic Purpura. NEJM 2007;357:2237
  14. Cheng et al. Eltrombopag for management of chronic immune thrombocytopenia (RAISE): a 6-month, randomised, phase 3 study. Lancet 2011;377:393
  15. Saleh et al. Safety and efficacy of eltrombopag for treatment of chronic immune thrombocytopenia: results of the long-term, open-label EXTEND study. Blood 2013;121:537
  16. Wong et al. Safety and efficacy of long-term treatment of chronic/persistent ITP with eltrombopag: final results of the EXTEND study. Blood 2017;130:2527(2+ years treatment with eltrombopag safe and effective)
  17. Gómez-Almaguer et al. Eltrombopag and high-dose dexamethasone as frontline treatment of newly diagnosed immune thrombocytopenia in adults. Blood 2014;123:3906 (12 month RFS 67% after 4 days of dex followed by 4 week course of eltrombopag)
  18. Pecci et al. Eltrombopag for the treatment of the inherited thrombocytopenia deriving from MYH9 mutations. Blood 2010;116:5832(11/12 patients responded)
  19. Rodeghiero et al. Thrombopoietin receptor agonists in hereditary thrombocytopenias. J Thromb Haemost 2018;16:1700
  20. McHutchison et al. Eltrombopag for Thrombocytopenia in Patients with Cirrhosis Associated with Hepatitis C. NEJM 2007;357:2227
  21. Cheloff and Al-Samkari. Avatrombopag for the treatment of immune thrombocytopenia and thrombocytopenia of chronic liver disease. J Blood Med 2019;10:313
  22. Afdhal et al. Eltrombopag Increases Platelet Numbers in Thrombocytopenic Patients With HCV Infection and Cirrhosis, Allowing for Effective Antiviral Therapy. Gastroenterology 2014;146:442(Higher platelet counts, higher incidence of liver decompensation and thrombosis in eltrombopag-treated patients)
  23. Moussa and Mowafy. Preoperative use of romiplostim in thrombocytopenic patients with chronic hepatitis C and liver cirrhosis. J Gastroenterol Hepatol 2013;28:335(33/35 patients had plts ≥ 70K with no bleeding or thrombosis)
  24. Olnes et al. Eltrombopag and improved hematopoiesis in refractory aplastic anemia. NEJM 2012;367:11(44% of patients had a hematologic response; minimal toxicity)
  25. Afdhal et al. Eltrombopag before procedures in patients with cirrhosis and thrombocytopenia. NEJM 2012;367:716(Treatment reduced need for platelet transfusion but increased risk of portal vein thrombosis)
  26. Mittelman et al. Eltrombopag for advanced myelodysplastic syndromes or acute myeloid leukaemia and severe thrombocytopenia (ASPIRE): a randomised, placebo-controlled, phase 2 trial. Lancet Haematol 2018;5:e34(Eltrombopag reduced platelet transfusion requirements and thrombocytopenia-related adverse events with acceptable safety profile)
  27. González-Porras et al. Use of eltrombopag after romiplostim in primary immune thrombocytopenia. Br J Haematol 2015;169:111(80% response rate)
  28. Zhou et al. A multicenter randomized open-label study of rituximab plus rhTPO vs rituximab in corticosteroid-resistant or relapsed ITP. Blood 2015;125:1541(Addition of rhTPO improved CR rate but not relapse rate)
  29. Liu et al. Thrombopoietin receptor agonists shift the balance of Fcγ receptors toward inhibitory receptor IIb on monocytes in ITP. Blood 2016;128:852(TPO agonists may reduce rate of platelet destruction in addition to promoting production)
  30. Kong et al. A novel recombinant human thrombopoietin therapy for the management of immune thrombocytopenia in pregnancy. Blood 2017;130:1097
  31. Visco et al. Eltrombopag for immune thrombocytopenia secondary to chronic lymphoproliferative disorders: a phase 2 multicenter study. Blood 2019;134:1708(78% response rate)
  32. Arnold et al. Perioperative oral eltrombopag versus intravenous immunoglobulin in patients with immune thrombocytopenia: a non-inferiority, multicentre, randomised trial. Lancet Haematol 2020;7:e640(78% of patients met platelet target vs 63% with IVIG; one patient had PE)
  33. Michel et al. Use of thrombopoietin receptor agonists for immune thrombocytopenia in pregnancy: results from a multicenter study. Blood 2020;136:3056(Good efficacy, no major adverse events with short-term use)
  34. Fattizzo et al. Thrombopoietin receptor agonists in adult Evans syndrome: an international multicenter experience. Blood 2022;140:789 (Effective, but high incidence of thrombosis, combination therapy often needed)
  35. Labrecque et al. Romiplostim drug presence in pregnancy and lactation. Blood 2023;141:2537
  36. Sun et al. Eltrombopag plus diacerein vs eltrombopag in patients with ITP: a multicenter, randomized, open-label phase 2 trial. Blood 2024;144:1791 (Diacerein not available in US)

Heparin-induced thrombocytopenia

Clinical features, risk factors

  1. Arepally GM. Heparin-induced thrombocytopenia. Blood 2017;129:2864
  2. Greinacher A. Heparin-induced thrombocytopenia. NEJM 2015;373:252
  3. Kelton and Warkentin. Heparin-induced thrombocytopenia: a historical perspective. Blood 2008;112:2607
  4. Warkentin TE.Heparin‐induced thrombocytopenia‐associated thrombosis: from arterial to venous to venous limb gangrene. J Thromb Haemost 2018;16:2128
  5. Selleng and Selleng. Heparin-induced thrombocytopenia in cardiac surgery and critically ill patients. Thromb Haemost 2016;116:843
  6. Warkentin and Kelton. Temporal aspects of heparin-induced thrombocytopenia. NEJM 2001;344:1286
  7. Oliveira et al. Incidence and prognostic significance of thrombocytopenia in patients treated with prolonged heparin therapy. Arch Intern Med 2008;168:94(36% incidence of thrombocytopenia – not all due to HIT – with heparin Rx for > 4d; increased risk of death, thrombotic and hemorrhagic events in affected pts)
  8. Girolami et al.  The incidence of heparin-induced thrombocytopenia in hospitalized medical patients treated with subcutaneous unfractionated heparin: a prospective cohort study. Blood 2003;101:2955
  9. McGowan et al. Reducing the hospital burden of heparin-induced thrombocytopenia: impact of an avoid-heparin program. Blood 2016;127:1954(Routine use of LMWH rather than UFH decreased incidence of HIT by 79% and incidence of HITT by 91%)
  10. Lubenow et al. The severity of trauma determines the immune response to PF4/heparin and the frequency of heparin-induced thrombocytopenia. Blood 2010;115:1797(HIT antibodies more common after major than minor surgery, and more common with UFH than LMWH)
  11. Warkentin et al. Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin. NEJM 1995;332:1330
  12. Prandoni et al. The incidence of heparin-induced thrombocytopenia in medical patients treated with low-molecular-weight heparin: a prospective cohort study . Blood 2005;106:3049
  13. Falvo et al. Heparin-associated thrombocytopenia in 24 401 patients with venous thromboembolism: findings from the RIETE Registry. J Thromb Haemost 2011;9:1761(Higher risk of HIT in patients treated with unfractionated heparin vs LMWH)
  14. Warkentin et al. Anti-platelet factor 4/heparin antibodies in orthopedic surgery patients receiving antithrombotic prophylaxis with fondaparinux or enoxaparin. Blood 2005;106:3791
  15. Bito et al. Mechanical prophylaxis is a heparin-independent risk for anti–platelet factor 4/heparin antibody formation after orthopedic surgery. Blood 2016;127:1036
  16. Warkentin et al. Gender imbalance and risk factor interactions in heparin-induced thrombocytopenia. Blood 2006;108:2937
  17. Warkentin et al. An Improved Definition of Immune Heparin-Induced Thrombocytopenia in Postoperative Orthopedic Patients. Arch Intern Med 2003;163:2518
  18. Warkentin et al. Anti-PF4/heparin antibodies and venous graft occlusion in postcoronary artery bypass surgery patients randomized to postoperative unfractionated heparin or fondaparinux thromboprophylaxis. J Thromb Haemost 2013;11:253(Risk of graft occlusion in SRA-negative patients)
  19. Welsby et al. The association of anti-platelet factor 4/heparin antibodies with early and delayed thromboembolism after cardiac surgery. J Thromb Haemost 2017;15:57(No impact of positive antibody test on thrombosis or survival)
  20. Warkentin and Sheppard. Serological investigation of patients with a previous history of heparin-induced thrombocytopenia who are reexposed to heparin. Blood 2014;123:2485(1/20 patients developed recurrent HIT; 8/20 seroconverted)
  21. Pishko et al. The risk of major bleeding in patients with suspected heparin‐induced thrombocytopenia. J Thromb Haemost 2019;17:1956 (Major bleeding in > 30% of suspected HIT cases, regardless of whether diagnosis confirmed or alternative anticoagulant used)

Pathophysiology of HIT

  1. Warkentin et al. Studies of the immune response in heparin-induced thrombocytopenia. Blood 2009;113:4963
  2. Padmanabhan et al. Heparin-independent, PF4-dependent binding of HIT antibodies to platelets: implications for HIT pathogenesis. Blood 2015;125:155(A subset of HIT antibodies recognize PF4 bound to platelet chondroitin sulfate; possible explanation for “delayed HIT”)
  3. Cines et al. Polyphosphate/platelet factor 4 complexes can mediate heparin-independent platelet activation in heparin-induced thrombocytopenia. Blood Adv 2016;1:62
  4. Rauova et al. Ultralarge complexes of PF4 and heparin are central to the pathogenesis of heparin-induced thrombocytopenia. Blood 2005;105:131
  5. Greinacher et al. The temporal profile of the anti-PF4/heparin immune response. Blood 2009;113:4970(rapid onset – 4-14 days – and spontaneous disappearance of IgG antibodies to heparin-PF4 in absence of prior heparin exposure is common pattern)
  6. Warkentin et al. Temporal presentations of heparin-induced thrombocytopenia following cardiac surgery: A single-center, retrospective cohort study. J Thromb Haemost 2022;20:2601 (Most patients developed antibodies 5-10 days after surgery; 10% had early presentation, attributed to recent heparin exposure)
  7. Khandelwal et al. The antigenic complex in HIT binds to B cells via complement and complement receptor 2 (CD21), Blood 2016;128:1789
  8. Dai et al. Dynamic intercellular redistribution of HIT antigen modulates heparin-induced thrombocytopenia. Blood 2018;132:727(PF4 redistributes from platelets to monocytes and endothelial cells; this may be a mechanim promoting thrombosis)
  9. Khandelwal et al. Polyreactive IgM initiates complement activation by PF4/heparin complexes through the classical pathway. Blood 2018;132:2431(“Naturally occurring” IgM promotes complement activation in response to heparin-PF4 complexes; response varies from patient to patient)
  10. Johnston et al. Recognition of PF4-VWF complexes by heparin-induced thrombocytopenia antibodies contributes to thrombus propagation. Blood 2020;135:1270
  11. Kames et al. ABO O blood group as a risk factor for platelet reactivity in heparin-induced thrombocytopenia. Blood 2022;140:274
  12. Rollin et al. Variable serotonin release assay pattern and specificity of PF4-specific antibodies in HIT, and clinical relevance. J Thromb Haemost 2022;20:2646 (Antibodies that activate platelets in the absence of heparin associated with more severe disease)

COVID-19 vaccine and HIT (VITT) and other HIT-related disorders

  1. Warkentin et al. Spontaneous heparin-induced thrombocytopenia syndrome: 2 new cases and a proposal for defining this disorder. Blood 2014;123:3651
  2. Greinacher et al. Autoimmune heparin-induced thrombocytopenia. J Thromb Haemost 2017;15:2099 (Pathophysiology and clinical features of atypical forms of HIT, characterized by heparin-independent platelet activation)
  3. Warkentin et al. Investigation of anti-PF4 versus anti-PF4/heparin reactivity using fluid-phase enzyme immunoassay for 4 anti-PF4 disorders: classic heparin-induced thrombocytopenia (HIT), autoimmune HIT, vaccine-induced immune thrombotic thrombocytopenia, and spontaneous HIT. J Thromb Haemost 2023;21:2268 (Antibodies in HIT variants typically react with PF4 alone as opposed to PF4/heparin in this assay)
  4. Schönborn et al. Anti-PF4 immunothrombosis without proximate heparin or adenovirus vector vaccine exposure. Blood 2023;142:2305
  5. Cines and Greinacher. Vaccine-induced immune thrombotic thrombocytopenia. Blood 2023;141:1659
  6. Arepally and Ortel. Vaccine-induced immune thrombotic thrombocytopenia: what we know and do not know. Blood 2021;138:293
  7. Greinacher et al. Insights in ChAdOx1 nCoV-19 vaccine-induced immune thrombotic thrombocytopenia. Blood 2021;138:2256 (Human cell-derived proteins in vaccine form complexes with PF4 on platelet surface, creating target for antibodies)
  8. Nazy et al. Recommendations for the clinical and laboratory diagnosis of VITT against COVID-19: Communication from the ISTH SSC Subcommittee on Platelet Immunology. J Thromb Haemost 2021;19:1585
  9. Thiele et al Frequency of positive anti-PF4/polyanion antibody tests after COVID-19 vaccination with ChAdOx1 nCoV-19 and BNT162b2. Blood 2021;138:299(6.8% incidence, most at low titer without platelet-activating ability)
  10. Schultz et al. Thrombosis and Thrombocytopenia after ChAdOx1 nCoV-19 Vaccination. NEJM 2021;384:2124(A version of “autoimmune” HIT after COVID vaccination)
  11. Greinacher et al. Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination. NEJM 2021;384:2092
  12. Tiede et al. Prothrombotic immune thrombocytopenia after COVID-19 vaccination. Blood 2021;138:350
  13. Scully et al. Pathologic Antibodies to Platelet Factor 4 after ChAdOx1 nCoV-19 Vaccination. NEJM 2021;384:2202
  14. Bourguignon et al. Adjunct Immune Globulin for Vaccine-Induced Immune Thrombotic Thrombocytopenia. NEJM 2021;385:720
  15. Patriquin et al. Therapeutic Plasma Exchange in Vaccine-Induced Immune Thrombotic Thrombocytopenia. NEJM 2021;385:857
  16. See et al. US Case Reports of Cerebral Venous Sinus Thrombosis With Thrombocytopenia After Ad26.COV2.S Vaccination, March 2 to April 21, 2021. JAMA 2021;325:2448
  17. Sánchez van Kamme et al. Frequency of Thrombocytopenia and Platelet Factor 4/Heparin Antibodies in Patients With Cerebral Venous Sinus Thrombosis Prior to the COVID-19 Pandemic. JAMA 2021;326:332.(Heparin-PF4 antibodies rare in non-vaccine-related CST)
  18. Salih et al. Vaccine-Induced Thrombocytopenia with Severe Headache. NEJM 2021;385:2103(Headache as presenting symptom of VIT without thrombosis)
  19. Pavord et al. Clinical Features of Vaccine-Induced Immune Thrombocytopenia and Thrombosis. NEJM 2021;385:1680
  20. See et al. Case Series of Thrombosis With Thrombocytopenia Syndrome After COVID-19 Vaccination—United States, December 2020 to August 2021. Ann Intern Med 2022;175:513
  21. Craven et al. Natural history of PF4 antibodies in vaccine-induced immune thrombocytopenia and thrombosis. Blood 2022;139:2553 (AntIbodies frequently persist for > 100 days; persistance associated with relapse risk)
  22. Schönborn et al. Most anti-PF4 antibodies in vaccine-induced immune thrombotic thrombocytopenia are transient.Blood 2022;139:1903
  23. Favoloro et al. Assessment of immunological anti-platelet factor 4 antibodies for vaccine-induced thrombotic thrombocytopenia (VITT) in a large Australian cohort: A multicenter study comprising 1284 patients. J Thromb Haemost 2022;20:2896 (ELISA may give false negative results – need functional assay to rule out)
  24. Schönborn et al. Long-term outcome in vaccine-induced immune thrombocytopenia and thrombosis. J Thromb Haemost 2023;21:2519
  25. Wang et al. VITT-like Monoclonal Gammopathy of Thrombotic Significance. NEJM 2025;392:995

Diagnosis of HIT

  1. Warkentin TE. Clinical picture of heparin-induced thrombocytopenia (HIT) and its differentiation from non-HIT thrombocytopenia. Thromb Haemost 2016;116:813
  2. Marchetti et al. Rapid and accurate Bayesian diagnosis of heparin-induced thrombocytopenia. Blood 2020;135:1171
  3. Raschke et al. Clinical effectiveness of a Bayesian algorithm for the diagnosis and management of heparin‐induced thrombocytopenia. J Thromb Haemost 2017;15:1640 (Combining EIA OD  with 4T score improves diagnostic accuracy)
  4. Nagler et al. Diagnostic value of immunoassays for heparin-induced thrombocytopenia: a systematic review and meta-analysis. Blood 2016;127:546
  5. Husseinzadeh et al. Diagnostic accuracy of IgG-specific versus polyspecific enzyme-linked immunoassays in heparin-induced thrombocytopenia: a systematic review and meta-analysis. J Thromb Haemost 2017;15:1203(IgG-specific assays more accurate)
  6. Padmanabhan et al. A Novel PF4-Dependent Platelet Activation Assay Identifies Patients Likely to Have Heparin-Induced Thrombocytopenia/Thrombosis. Chest 2016;150:506(With editorial)
  7. Bannow et al. A prospective, blinded study of a PF4-dependent assay for HIT diagnosis. Blood 2021; 137:1082(Assay performs as well as SRA)
  8. Warkentin et al. High sensitivity and specificity of an automated IgG-specific chemiluminescence immunoassay for diagnosis of HIT. Blood 2018;132:1345
  9. Warkentin et al. Prevalence and Risk of Preexisting Heparin-Induced Thrombocytopenia Antibodies in Patients With Acute VTE. Chest 2011; 140:366(Positive SRA assay predicts rapid-onset HIT; positive EIA with negative SRA does not)
  10. Cuker et al. Predictive value of the 4Ts scoring system for heparin-induced thrombocytopenia: a systematic review and meta-analysis. Blood 2012;120:4160(“A low probability 4Ts score appears to be a robust means of excluding HIT”)
  11. Cuker et al. The HIT Expert Probability (HEP) Score: a novel pre‐test probability model for heparin‐induced thrombocytopenia based on broad expert opinion. J Thromb Haemost 2010;8:2642
  12. Linkins et al. Combination of 4Ts score and PF4/H-PaGIA for diagnosis and management of heparin-induced thrombocytopenia: prospective cohort study. Blood 2015;126:597(4Ts score <4, negative rapid immunoassay → no HIT)
  13. Warkentin et al. Serotonin‐release assay‐negative heparin‐induced thrombocytopenia. Am J Hematol 2020;95:38(Sensitivity of SRA for HIT about 97%)
  14. Nazy et al. Platelet‐activating immune complexes identified in critically ill COVID‐19 patients suspected of heparin‐induced thrombocytopenia. J Thromb Haemost 2021;19:1342(Mimics HIT)
  15. Brodard et al. COVID‐19 patients often show high‐titer non‐platelet‐activating anti‐PF4/heparin IgG antibodies. J Thromb Haemost 20221;19:1294

Treatment of HIT

  1. Cuker et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia. Blood Adv 2018;2:3392
  2. Linkins et al. Treatment and Prevention of Heparin-Induced Thrombocytopenia. Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141:e495S
  3. Cuker and Cines. How I treat heparin-induced thrombocytopenia. Blood 2012;119:2209
  4. Aljabri et al. Cost-effectiveness of anticoagulants for suspected heparin-induced thrombocytopenia in the United States. Blood 2016;128:3043(Fondaparinux more cost-effective than argatroban or bivalirudin)
  5. Cuker A. Management of the multiple phases of heparin-induced thrombocytopenia. Thromb Haemost 2016;116:835
  6. Kelton et al. Nonheparin anticoagulants for heparin-induced thrombocytopenia. NEJM 2013;368:737
  7. Joseph et al. Bivalirudin for the treatment of patients with confirmed or suspected heparin-induced thrombocytopenia. J Thromb Haemost 2014;12:1044
  8. Lewis et al. Effects of Argatroban Therapy, Demographic Variables, and Platelet Count on Thrombotic Risks in Heparin- Induced Thrombocytopenia. Chest 2006;129:1407
  9. Levine et al. Argatroban Therapy in Heparin-Induced Thrombocytopenia With Hepatic Dysfunction. Chest 2006;129:1167
  10. Keyl et al. Argatroban pharmacokinetics and pharmacodynamics in critically ill cardiac surgical patients with suspected heparin-induced thrombocytopenia. Thromb Haemost 2016;115:1081(Drug half-life markedly increased in critically ill cardiac pts)
  11. Kang et al. Fondaparinux for the treatment of suspected heparin-induced thrombocytopenia: a propensity score–matched study. Blood 2015;125:924(Retrospective study; fondaparinux associated with similar bleeding rates and somewhat lower thrombosis rates than alternative therapies)
  12. Tuleja et al. Cost-effectiveness analysis of alternative anticoagulation in suspected heparin-induced thrombocytopenia. Blood Adv 2022;6:3114 (Fondaparinux superior to argatroban)
  13. Warkentin et al. Direct oral anticoagulants for treatment of HIT: update of Hamilton experience and literature review. Blood 2017;130:1104(DOACs appear effective in HIT)
  14. Nasiripour et al. Dabigatran as a Treatment Option for Heparin‐Induced Thrombocytopenia. J Clin Pharmacol 2018;50:107
  15. Farasatinasab et al. Rivaroxaban as an Alternative Agent for Heparin-Induced Thrombocytopenia. J Clin Pharmacol 2020 (Epub)
  16. Skeith L. Anticoagulating patients with high-risk acquired thrombophilias. Blood 2018;132:2219(Discusses DOAC use in APS, HIT, PNH)
  17. Padmanabhan et al. IVIg for Treatment of Severe Refractory Heparin-Induced Thrombocytopenia. Chest 2017;152:478(Small case series describing rapid and sustained responses to IVIG in refractory HIT; with editorial)
  18. Warkentin et al. High-dose intravenous immunoglobulin G and usual heparin anticoagulation for urgent cardiac surgery in a patient with severe autoimmune heparin-induced thrombocytopenia. J Thromb Haemost 2025;23:321
  19. Arcinas et al. Autoimmune heparin‐induced thrombocytopenia and venous limb gangrene after aortic dissection repair: in vitro and in vivo effects of intravenous immunoglobulin. Transfusion 2019;59:1924
  20. Warkentin and Anderson. How I treat patients with a history of heparin-induced thrombocytopenia. Blood 2016;128:348
  21. Selleng et al. Management of anticoagulation in patients with subacute heparin-induced thrombocytopenia scheduled for heart transplantation. Blood 2008;112:4024(safe to give limited course of UFH if functional assay for heparin Ab negative)
  22. Pollak U. Heparin‐induced thrombocytopenia complicating extracorporeal membrane oxygenation support: Review of the literature and alternative anticoagulants. J Thromb Haemost 2019;17:1608

Thrombocytopenia in pregnancy

  1. Fogerty and Kuter. How I treat thrombocytopenia in pregnancy. Blood 2024;143:747
  2. Cines and Levine. Thrombocytopenia in pregnancy. Blood 2017;130:2271
  3. Yang et al. Genetic basis of pregnancy-associated decreased platelet counts and gestational thrombocytopenia. Blood 2024;143:1528
  4. Reese et al. Platelet Counts during Pregnancy. NEJM 2018;379:32(Platelets <150K in 10% of uncomplicated pregnancies; count <100K should prompt evaluation for other cause of thrombocytopenia)
  5. Webert et al.  A retrospective 11-year analysis of obstetric patients with idiopathic thrombocytopenic purpura. Blood 2003;102:4306
  6. Sun et al. Corticosteroids compared with intravenous immunoglobulin for the treatment of immune thrombocytopenia in pregnancy. Blood 2016;128:1329(Many did not need treatment, IVIG and steroids produced similar good outcomes in this retrospective study)
  7. Moatti-Cohen et al. Unexpected frequency of Upshaw-Schulman syndrome in pregnancy-onset thrombotic thrombocytopenic purpura. Blood 2012;119:5888

Post-transfusion purpura; neonatal alloimmune purpura

  1. Kickler et al. Studies on the pathophysiology of posttransfusion purpura. Blood 1986; 68:347
  2. Ghevaert et al. Recombinant HPA-1a antibody therapy for treatment of fetomaternal alloimmune thrombocytopenia: proof of principle in human volunteers. Blood 2012;122:313
  3. Winkelhorst et al. Antenatal management in fetal and neonatal alloimmune thrombocytopenia: a systematic review. Blood 2017;129:1538

Drug-induced immune thrombocytopenia

  1. Fuentes et al. An updated list of drugs suspected to be associated with immune thrombocytopenia based on the WHO pharmacovigilance database.  Blood 2022;140:922
  2. George and Aster. Drug-induced thrombocytopenia: pathogenesis, evaluation, and management. Hematology 2009;153
  3. Bougie et al. Mechanism of quinine-dependent monoclonal antibody binding to platelet glycoprotein IIb/IIIa. Blood 2015;126:2146(Drug binds to antibody, increasing its affinity for platelet antigen)
  4. Reese et al. Identifying drugs that cause acute thrombocytopenia: an analysis using 3 distinct methods. Blood 2010;116:2127
  5. Arnold et al. A systematic evaluation of laboratory testing for drug-induced immune thrombocytopenia. J Thromb Haemost 2013;11:169(Drugs most likely: quinine, quinidine, TMP/sulfa, vancomycin, penicillin, rifampin, carbamazepine, ceftriaxone, ibuprofen, mirtazapine, oxaliplatin, suramin, abciximab, tirofiban and eptifibatide)
  6. Aster and Bougie. Current concepts: drug-induced immune thrombocytopenia. NEJM 2007;357:580
  7. Warkentin T. Drug-induced immune-mediated thrombocytopenia – from purpura to thrombosis. (Editorial) NEJM 2007;356:891
  8. George et al. Drug-induced thrombocytopenia: a systematic review of published case reports. Ann Intern Med 1998;129:886
  9. Bougie et al. Patients with quinine-induced immune thrombocytopenia have both “drug-dependent” and “drug-specific” antibodies. Blood 2006;108:922
  10. Liles et al. Diversity and severity of adverse reactions to quinine: A systematic review. Am J Hematol 2016 (Epub)(20% of reactions to quinine-containing beverages, lifethreatening multisystem illness common)
  11. Von Drygalski et al. Vancomycin-mediated immune thrombocytopenia. NEJM 2007; 356:904
  12. Greinacher et al. Megakaryocyte impairment by eptifibatide-induced antibodies causes prolonged thrombocytopenia. Blood 2009;114:1250
  13. Cuker et al. A distinctive form of immune thrombocytopenia in a phase 2 study of alemtuzumab for the treatment of relapsing-remitting multiple sclerosis. Blood 2011;118:6299(Delayed presentation, severe thrombocytopenia, responsive to standard treatment, prolonged remission)
  14. Bakchoul et al. Protamine (heparin)-induced thrombocytopenia: a review of the serological and clinical features associated with anti-protamine/heparin antibodies. J Thromb Haemost 2016;14:1685
  15. Curtis et al. Patients treated with oxaliplatin are at risk for thrombocytopenia caused by multiple drug-dependent antibodies. Blood 2018;131:1486

Other acquired thrombocytopenias

  1. Saito et al. Hypomegakaryocytic thrombocytopenia (HMT): an immune-mediated bone marrow failure characterized by an increased number of PNH-phenotype cells and high plasma thrombopoietin levels. Br J Haem 2016;175:246
  2. Kyrle and Eichinger. How I manage cyclic thrombocytopenia. Blood 2021;137:178
  3. Warkentin et al. Platelet-Endothelial Interactions: Sepsis, HIT, and Antiphospholipid Syndrome. Hematology 2003:497-519
  4. Claushuis et al. Thrombocytopenia is associated with a dysregulated host response in critically ill sepsis patients. Blood 2016;127:3062
  5. Drews and Weinberger. Thrombocytopenic disorders in critically ill patients. Am J Respir Crit Care Med 2000;162:347
  6. Cole et al. Ineffective platelet production in thrombocytopenic human immunodeficiency virus-infected patients. Blood 1998;91:3239
  7. Greinacher and Selleng. How I evaluate and treat thrombocytopenia in the intesive care unit. Blood 2016;128:3032
  8. Alhamdi et al. Histone-associated thrombocytopenia in patients who are critically ill. JAMA 2016;315:817
  9. Ando et al. New insights into the thrombopoietic status of patients on dialysis through the evaluation of megakaryocytopoiesis in bone marrow and of endogenous thrombopoietin levels. Blood 2001;97:915
  10. Kiaii et al. Use of electron-beam sterilized hemodialysis membranes and risk of thrombocytopenia. JAMA 2011;306:1679
  11. McHutchison et al. Eltrombopag for Thrombocytopenia in Patients with Cirrhosis Associated with Hepatitis C. NEJM 2007;357:2227
  12. Chiao et al. Risk of Immune Thrombocytopenic Purpura and Autoimmune Hemolytic Anemia Among 120 908 US Veterans With Hepatitis C Virus Infection. Arch Intern Med 2009;169:357
  13. Bat et al. Thrombopoietic status of patients on hemodialysis. Br J Haematol 2016;172:954(Higher TPO levels and increased proportion of immature platelets in dialysis patients suggest shortened platelet lifespan)
  14. Skeith et al. A practical approach to evaluating postoperative thrombocytopenia. Blood Adv 2020;4:776
  15. Ayad et al. Long-term risk of developing immune thrombocytopenia and hematologic neoplasia in adults with mild thrombocytopenia. Blood 2022;140:2849 (19x higher risk of developing ITP or heme malignancy during 15-yr followup vs controls)