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• Thrombocytopenia


  Most common cause of abnormal bleeding, defined as a platelet count less than 150 × 109/L
• Classification of Thrombocytopenia


  • Impaired or Decreased production
  • Increased loss/destruction
  • Abnormalities in Distribution or Dilution

  
• Impaired/Decreased Production of Platelets


  • Decreased Megakaryocytes in the BM
  • Ineffective Thrombopoiesis
  • Miscellaneous Conditions

  
• Congenital causes of impaired/decreased platelet production


  • May-Hegglin anomaly
  • Bernard-Soulier syndrome
  • Fechtner syndrome
  • etc.

  
• May-Hegglin anomaly


  Rare, autosomal dominant condition with mutation in MYH9 gene that encodes nonmuscle myosin heavy chain (platelet cytoskeletal protein), leading to large platelets, thrombocytopenia, and Dohle-like bodies in neutrophils
• TAR syndrome


  Thrombocytopenia with absent radii; bilateral radial aplasia/hypoplasia, autosomal recessive (mutation and/or deletion in RBM8A gene), manifests with cardiac lesions, transient leukemoid reactions, and platelet count 10-30×109/L in infancy increasing over time
• Neonatal Thrombocytopenia is present in 1-5% of infants at birth, caused by infection, maternal drug ingestion, impaired production, increased sequestration, or DIC
• Drug-Induced Hypoplasia


  Chemotherapeutic agents, chronic ethanol abuse, and other drugs suppress BM megakaryocyte production
• Ineffective Thrombopoiesis


  Normal to increased megakaryocytes but decreased circulating platelets, due to defective platelet formation or destruction in the BM, found in vitamin B12/folate deficiency, thrombopoietin deficiency, PNH, and viral infections

  
• Infiltration of BM by Malignant Cells


  Marrow replacement and toxins produced by abnormal cells, seen in myelophthisic processes like metastatic cancer, myeloma, myelofibrosis, and leukemia
• Viral Infection


  Cause thrombocytopenia by acting on megakaryocytes or circulating platelets, directly or through viral antigen-antibody complexes

  
• Causes of Increased Platelet Destruction

  • Immunologic (Autoimmune, Drug-induced, Isoimmune)
  • Nonimmunologic (Loss, Consumption)

  
• Immune Thrombocytopenic Purpura (ITP)


  Autoimmune disorder causing thrombocytopenia in the absence of any other disease, with two forms: Acute ITP in children and Chronic ITP in adults

  
• Acute ITP


  • Disorder of children, abrupt onset of bruising, petechiae, and mucosal bleeding, self-limiting, most recover in 3 weeks
• Chronic ITP


  • Can occur at any age, more common in females 20-50 years old, fluctuating clinical course, increased platelet IgG
• Immunologic Drug-Induced Thrombocytopenia


  Antibody production when exposed to a given drug, can be drug-dependent, hapten-induced, drug-induced autoantibodies, or immune complex-induced

  
• Neonatal Alloimmune Thrombocytopenia (NAIT)


  Develops when the mother lacks a platelet-specific antigen that the fetus has inherited from the father, can cause clinically significant thrombocytopenia
• Neonatal Autoimmune Thrombocytopenia


  Due to passive transplacental transfer of antibodies from a mother with ITP or SLE, newborns have normal to decreased platelet at birth with progressive decrease for about 1 week before platelets increase
• Posttransfusion Purpura (PTP)


  Rare, develops about 1 week after transfusion of platelet-containing blood products, recipient's plasma contain alloantibodies to antigens on blood product's platelets
• Thrombocytopenia in Pregnancy and Preeclampsia


  Incidental Thrombocytopenia of Pregnancy is the most common cause, cause unknown, Preeclampsia and other hypertensive disorders can also cause thrombocytopenia
• Thrombotic Thrombocytopenic Purpura (TTP)


  Deficiency in ADAMTS 13 (a vWF-cleaving protease) leads to formation of hyaline thrombi (platelets + VWF) in capillaries and arterioles throughout the body

  
• Anti-HPA-1a


  Antibodies to antigens on blood product's platelets, which the recipient does not have

  
• Antibodies to GPIIb/IIIa receptor complex


  Antibodies to antigens on blood product's platelets, which the recipient does not have

  
• Incidental Thrombocytopenia of Pregnancy


  aka pregnancy-associated thrombocytopenia and gestational thrombocytopenia
• Incidental Thrombocytopenia of Pregnancy

  Most common cause of thrombocytopenia in pregnancy
• Cause of Incidental Thrombocytopenia of Pregnancy is unknown
• Preeclampsia and other hypertensive disorders of pregnancy

  Mechanism of platelet destruction is unclear

  
• After delivery, the thrombocytopenia usually resolves in a few days
• Thrombotic Thrombocytopenic Purpura (TTP)


  aka Moschcowitz syndrome

  
• ADAMTS 13


  a vWF-cleaving protease
• ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) deficiency leads to accumulation of ultra-large von Willebrand factor (ULVWF) multimers

  
• TTP


  • Triad of MAHA, thrombocytopenia, and neurologic abnormalities
  • Pentad: + fever and renal dysfunction
• Plasma exchange


  Most effective treatment for TTP using FFP or cryoprecipitate-poor plasma
• Clinical-neuroimaging analysis of TTP patients revealed a variety of brain lesions including reversible cerebral edema lesions with MRI features of reversible posterior leukoencephalopathy syndrome (RPLS)

  
• Hemolytic Uremic Syndrome (HUS)


  Occurs in children after gastrointestinal infection with Shigella dysentariae serotypes and E. coli serotype O157:H7
• Hemolytic Uremic Syndrome (HUS)


  • Toxins enter bloodstream and attach to renal glomerular cells
  • Cardinal signs: hemolytic anemia, renal failure, and thrombocytopenia
  • Intravascular clotting is confined in the kidney
  • Lack of neurologic symptoms
• Artificial surfaces


  Cardiovascular prosthetic device, prosthetic vascular grafts, and dialysis membranes
• Artificial surfaces


  • Induce platelet adherence and formation of platelet microaggregates

  
• Disseminated Intravascular Coagulation (DIC)


  Activation of the coagulation system
• Disseminated Intravascular Coagulation (DIC)


  • Leads to intravascular thrombin generation, platelet aggregation and CF consumption