Thrombocytopenia

Thrombocytopenia 
 
Mechanism 
  • Decreased bone marrow production 
    • Marrow aplasia 
    • Fibrosis 
    • Infiltration with malignant cells 
    • Cytotoxic drugs 
    • Impair megakaryocyte proliferation and maturation 
    • Sepsis- Viral and bacterial infections 
    • Alcohol 
    • B12/Folate deficiency 
  • Increased splenic sequestrationEnlargement of spleen causes fraction of sequestered platelets to increase, decreasing the platelet count. Most common causes of splenomegaly are portal hypertension secondary to liver disease, congestive splenomegaly and splenic infiltration with tumor cells in myeloproliferative or lymphoproliferative disorders 
  • Increased destruction of platelets 
    • Fibrin thrombi
    • Intravascular prostheses 
    • HELLP syndrome 
    • Transfusion reactions
  • Increased platelet consumption 
    • Vasculitis 
    • Hemolytic uremic syndrome 
    • Thrombotic thrombocytopenic purpura 
    •  DIC 
    • Sepsis  
  • Immunologic thrombocytopenia (ITP)Platelets coated with antibody, immune complexes, or complements are rapidly cleared by mononuclear phagocytes in the spleen or other tissue. common causes are ITP,  viral or bacterial infection and drugs like heparin
  • Drug-induced thrombocytopenia : heparin can cause HITT. Alcohol can supress bone marrow. 
Laboratory Tests 
  • Complete blood count with evaluation of peripheral smear. If platelets clumped on peripheral smear , redraw in sodium citrate or heparin. 
  • HITT: Patients with HIT can be recognized by their decreasing platelet count in the setting of thrombosis while receiving therapeutic doses of heparin. The 4 “T”s have been recommended for use in a diagnostic algorithm for HIT. 
    • Thrombocytopenia with platelet count fall >50% and platelet nadir ≥20
    • Timing of platelet count drop is 5–14 days. It occurs before 5 days only in those who were exposed to heparin in the prior few weeks or months (< ~100 days) and have circulating antiheparin/PF4 antibodies. Rarely, thrombocytopenia and thrombosis begin several days after all heparin has been stopped (delayed-onset HIT can occur upto 30 days after stopping heparin). 
    • New thrombosis or skin necrosis
    • No other causes of thrombocytopenia
  • Assays to detect HIT are Antiheparin/PF4 antibodies . Should confirm with SRA or platelet aggregation tests 
Imaging 
  • Ultrasonography, CT, or radionuclide scan to evaluate for splenomegaly or accessory spleens may be indicated. 
  • In patients diagnosed with HIT, imaging studies to evaluate the presence of thrombosis (at least lower-extremity duplex) are recommended because presence or absence of thrombosis decides the duration of treatment. 
Diagnostic Procedures 
  • Bone marrow aspiration or biopsy recommended for patients not responsive to therapy 
Treatment Approach 
  • For drug-induced thrombocytopenia, stop use of the offending drug. Patients with platelet counts < 10,000–20,000/μL and severe hemorrhage may require: 
    • Temporary support with glucocorticoids 
    • Plasmapheresis 
    • Platelet transfusions 
  • ​ HIT 
    • Stop heparin treatment. 
    • Reverses both thrombocytopenia and heparin-induced thrombosis 
    • Cannot substitute low-molecular-weight heparin for unfractionated heparin in patient with HIT
    • Should be anticoagulated for atleast 100 days even in the absence of thrombosis because of the high rate of thrombosis in patients with HIT. ( Antibody persists for 100 days)  
    • Drug of choice are Argatroban,  Lepirudin,  Bivalirudin,  Fondaparinux. Introduction of warfarin alone in the setting of HIT or HITT may precipitate thrombosis, particularly venous gangrene. Warfarin should be started only after alternative anticoagulation has been given for several days and the prothrombotic state has lessened and platelet counts improved to at least >150.  Intial warfarin dose should not exceed 5mg per day.  
    • Platelet transfusions should be avoided due to increased risk of thrombosis 
 
PEARLS: 
  • In patients with a history of HIT in whom heparin antibodies have been shown to be absent who require cardiac surgery, we suggest the use of heparin (short-term use only) over nonheparin anticoagulants.  
  • ITP: treat with 1 gm Solumedrol daily. Other options include IvIG, plasmapheresis and splenectomy. 
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