thrombocytopenia

see also:

• full blood examination (FBE)
• thrombocytosis

• thrombocytopenia is defined by an excessively low concentration of platelets in the peripheral blood < 150 x 10^9/L
• platelets are formed by fragmentation of megakaryocytes, most of which occurs in the lungs and not the bone marrow as was thought ¹⁾ and circulate in the blood for 7-10 days
• bleeding time is generally not prolonged until the platelet count is below 100,000/µL
• platelet counts from 20,000/µL to 50,000/µL, petechiae and ecchymoses are observed following mild trauma
• platelet counts below 20,000/µL pose significant risks of major spontaneous haemorrhage
• platelet counts below 10,000/µL, the risk of spontaneous mucocutaneous bleeding (gingival bleed, epistaxis, menorrhagia, petechiae and ecchymoses) and life threatening, spontaneous intracranial haemorrhage or gastrointestinal bleeding increases rapidly
• the risk of bleeding is also dependent upon presence of functional platelet defects

• artefactual or pseudothrombocytopenia
  • accounts for ~15% of cases in ambulatory patients
  • this is caused by in vitro clumping of platelets when ethylenediaminetetraacetic acid (EDTA) is used as an anticoagulant
• dilutional
• 5% of the normal population will fall outside the “normal range” by definition

• hypersplenism
  • counts rarely fall below 40,000/µL
  • portal hypertension in chronic liver disease²⁾
• immune-mediated:
  • Idiopathic thrombocytopenic purpura (ITP)
    • esp. well young women
    • acute
    • chronic
    • Evans syndrome: ITP with autoimmune haemolytic anaemia
  • heparin-induced thrombocytopenia (HIT)
    • Type 1 HIT is a modest transient decrease in platelet counts that occurs within the first 2 to 3 days after heparin initiation and returns to normal spontaneously, even with continuation of heparin
    • Type 2 HIT is less common, seen in about 0.3 to 5% of patients caused by antibodies against platelet factor 4-heparin complex, usually occurs 4 to 14 days after heparin initiation. Abnormal thrombosis, sometimes catastrophic, is the predominant manifestation of HIT and bleeding is uncommon. Cease heparin and do not use LMW heparin. - see also thrombosis with thrombocytopenia syndrome (TTS / VITT / VIPIT)
  • thrombosis with thrombocytopenia syndrome (TTS / VITT / VIPIT)
  • drug-induced antibodies
    • GPIIb/IIIa inhibitor related
      • unlike other drug-induced thrombocytopenias, GPIIb/IIIa inhibitor-induced thrombocytopenia develops within 24 hours of exposure
  • HIV / AIDS
  • autoimmune hepatitis, primary biliary cholangitis and chronic hepatitis C virus infection
  • post-transfusion purpura
    • rare, mostly in women, it presents as severe thrombocytopenia 5 to 10 days after red cells or platelet transfusion
  • HELLP in pregnant patients
  • gestational thrombocytopenia occurs in 5% near delivery
• connective tissue (CT) disorders such as systemic lupus erythematosus (SLE), rheumatoid arthritis and antiphospholipid antibody disorder
• paroxysmal nocturnal haemoglobinuria
• non-immune:
  • disseminated intravascular coagulation (DIC)
  • sepsis / septicaemia
  • cardiac valves
  • pre-eclampsia and eclampsia
  • thrombotic thrombocytopenic purpura (TTP) and haemolytic uraemic syndrome (HUS)
    • also have microangiopathic hemolytic anemia (schistocytes, elevated LDH, and indirect hyperbilirubinemia)
    • may also have neurologic abnormalities, fever, and renal disease
    • may be related to clopidogrel or ticlopidine
    • caused by deficiency (due to autoantibodies) of von Willebrand factor-cleaving protease known as ADAMTS13 leads to accumulation of large multimers of von Willebrand factor which cause spontaneous platelet aggregation and thrombi
    • emergent plasma exchange is the cornerstone of TTP treatment
  • Kasabach Merrit syndrome

• haematologic malignancies
• aplastic anaemia
• myelodysplasia
• chronic liver disease
• drugs:
  • cytotoxic agents
    • with most chemotherapy agents, nadir blood count occurs 7 to 10 days after chemotherapy and recovery over 2 to 3 weeks
    • certain agents like mitomycin can also cause TTP
  • ethanol (alcohol and alcohol withdrawal)
  • chloramphenicol
  • diuretics
  • sodium valproate (Epilim)
• Ionising radiation
• HIV / AIDS
• EBV / glandular fever / infectious mononucleosis, cytomegalovirus (CMV), varicella-zoster virus (chickenpox/shingles), mumps, rubella, parvovirus
• Salmonella typhi (typhoid enteric fever)
• dengue fever
• rare infections such as:
  • Babesiosis
  • Anaplasmosis
• Severe fever with thrombocytopenia syndrome virus (SFTSV)
• vitamin D deficiencies
• folate deficiency
• hereditary thrombocytopenias
  • Congenital amegakaryocytic thrombocytopenia
  • Thrombocytopenia absent radius syndrome
  • Fanconi anemia
  • Bernard-Soulier syndrome, associated with large platelets
  • May-Hegglin anomaly, the combination of thrombocytopenia, pale-blue leuckocyte inclusions, and giant platelets
  • Grey platelet syndrome
  • Alport syndrome
  • Wiskott–Aldrich syndrome
• metastatic tumours to bone marrow

• exclude artefactual cause ⇒ repeat full blood examination (FBE)
• if within 4-20 days of an Astra-Zeneca Covid-19 vaccine then investigate for possible thrombosis with thrombocytopenia syndrome (TTS / VITT / VIPIT)
• if neutropenia and/or anaemia as well then ?aplastic anaemia
• is patient pregnant?
  • LFT's ⇒ ?HELPP vs gestational vs ITP
• history - PH ITP, drugs, heparin, chemotherapy, cancer, etc.
• examination - evidence of bleeding, splenomegaly,
• if febrile, search for underlying illness eg. sepsis, TTP, viral infections, typhoid, etc
• check full blood examination (FBE) smear:
  • platelet clumps ⇒ artefactual
  • giant platelets ⇒ hereditary thrombocytopenia
  • schistocytes or spherocytes ⇒ look for haemolysis (LDH, bilirubin) and if confirmed:
    • Direct Coombs
      • +ve: Evans syndrome
      • -ve: check for disseminated intravascular coagulation (DIC), if negative then ?thrombotic thrombocytopenic purpura (TTP)
  • suspicious smear for primary marrow disorder ⇒ bone marrow Bx
    • nucleated red cells
    • bilobed neutrophils
    • macrocytosis
    • blasts
  • isolated thrombocytopenia
    • ?chemotherapy-induced
    • ?drug-induced (eg. heparin) ⇒ cease drug and platelet count should recover in 5-7days
    • ?Idiopathic thrombocytopenic purpura (ITP)
    • consider bone marrow biopsy

• platelet count < 10,000/µL
• platelet count < 20,000/µL plus presence of bleeding, fever, infection, platelet function defect, or coagulopathy
• platelet count < 50,000/µL prior to minor procedures, in actively anticoagulated patients or in the presence of active bleeding
• platelet count < 75,000/µL prior to general surgery
• platelet count < 100,000/µL prior to neurologic or ophthalmologic surgery³⁾