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Thrombocytopenia

Thrombocytopenia review

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Thrombocytopenia

  1. 1. Diana Girnita, MD, PhD The Christ Hospital December 2011
  2. 2. Definition  Platelets < 150,000/ml  2.5% of normal people < 150,000/ml  Recent drop ≥ 50%, even if normal platelets count
  3. 3. Increased risk of bleeding if < 60,000 -with minor trauma if < 12,000 –spontaneous If < 6,000 - severe, life threatening
  4. 4. Initial approach of the patient  Clinical: 1. epistaxis 2. gingival bleeding 3. meno/ metrorrhagia 4. tend to bleed immediately after minor trauma 5. cerebral bleeding  Cutaneous: petechiae, purpura, ecchymoses
  5. 5. Clinical presentation A: Dense, cutaneous petechiae on the foot and ankle. B:Bullous hemorrhages on the buccal mucosa PURPURA - purplish discoloration of the skin due to the presence of confluent petechiae Ecchymoses — nontender areas of bleeding into the skin, usually associated with multiple colors
  6. 6. PMH ?Bleeding history ?Hematologic disease (acute /chronic leukemias, MDS) ?Recent new drugs or drugs that are only taken intermittently (ASA, NSAID, herbal, plavix, heparin) ?Recent live virus vaccination ?Recent infection (viral, bacterial, rickettsial) /sepsis ?Recent travel — malaria /dengue virus, leptospirosis, meningococcemia, hantavirus, hemorrhagic fevers (eg, Ebola, Lassa ).
  7. 7. PMH- cont ?Recent massive transfusion (PRBCs /platelets) in an allo-sensitized recipient ? Recent organ transplantation by sensitization to platelet allo-antigens /GVHD ?Pregnancy especially late in the 3rd trimester or at onset of labor , +/- ITP or TTP-HUS, or preeclampsia/ eclampsia FH: ++ for bleeding and/or thrombocytopenia
  8. 8. The physical examination  Examination in critical areas 1. Ocular fundus -CNS bleeding 2. Lymphadenopathy 3. Hepatosplenomegaly 4. Stool for occult blood 5. Skin -feet and ankles , presacral area, areas of previous trauma  Outline areas of bleeding with a marking pen (changes in the number/pattern of petechiae)
  9. 9. Labs  CBC -WBC, RBC, Plt count -r/o TTP and acute leukemia  PERIPHERAL SMEAR  Plt #  Ptl morphology- large?  +/- Plt clumping  +/- scystocytes  If anemia: ? Hemolytic ?  (LDH, haptoglobin, Bilirubin)
  10. 10. Bone marrow examination  Evaluate megakariocytes  BM could be  Hypocellular  Cellular  BM replacement
  11. 11. Mechanisms of thrombocytopenia 1. Pseudothrombocytopenia 2. Decreased platelet production 3. Increased platelet destruction 4. Dilutional thrombocytopenia 5. Distributional thrombocytopenia
  12. 12. Pseudothrombocytopenia  EDTA-induced platelet clumping  Drugs –Abciximab - directed against the GP IIb/IIIa receptor
  13. 13. Decreased platelet production  Hypocellular BM  Infections (MMR, varicella, parvovirus, hepatitis C EBV, HIV, rickettias)  Live attenuated vaccines •Drugs •Aplastic anemia •Alcohol •Autoantibody - against the thrombopoietin receptor (SLE)
  14. 14. Decreased platelet production  Cellular BM  Leukemias  MDS  Severe vit B12 /folate deficient anemia MDS
  15. 15. Decreased platelet production  Marrow replacement  Myelofibrosis  Solid malignancies  Granulomas Myelofibrosis
  16. 16. Increased platelet destruction 1.Immune –mediated  Primary ITP  Secondary: infectious, CLL, drugs (heparin), APL sdr, lymphoma  Allo-immunization (post-transfusion) 2. Non-immune mediated  MAHA (TTP-HUS, DIC)  Evan Sdr: thrombocytopenia + hemolytic anemia  Vascular prostheses/ bypass; trauma  Drugs: ticlopidine/clopidogrel,  Cavernous hemangioma  HELLP syndrome -in pregnant women
  17. 17. Other causes:  Dilutional thrombocytopenia — massive blood transfusion with PRBC (> 20 units of PRBCs /24H)  Distributional thrombocytopenia caused by splenic sequestration Portal hypertension Cirrhosis Splenomegaly Hypothermia
  18. 18. Thrombocytopenia in the ICU patient  Sepsis/septic shock - one-half of the cases  Use of heparin  DIC  Massive blood transfusion  Post-transfusion purpura  Cardiopulmonary resuscitation  Cardiopulmonary bypass  ARDS  PE  Use of intravascular catheters  Solid organ allograft rejection  Drugs (antibiotics, chemotherapy, antiplatelet agents - abciximab)
  19. 19. Heparin induced thrombocytopenia (HIT) HIT I HIT II
  20. 20. HIT II  an immune-mediated disorder characterized by the formation of antibodies against the heparin-platelet factor 4 complex.  UFH/LMWH  5-10 days after the heparin is started  Heparin –PF4 complex- Ab induce platelet aggregation and activation, endothelial cell activation (IL-6, vWF)  Thrombosis (arterial and venous) + thrombocytopenia (>50% fall in Plt)  DVT, PE (25%)  Skin necrosis at injection site
  21. 21. Dg of HIT II  Serotonin release assay  Heparin-induced platelet aggregation  The solid phase ELISA immunoassay- heparin-PF4- IgG antibodies
  22. 22. Treatment HIT II  Stop the heparin UFH/LMWH  Lepirudin — Refludan®  Is a recombinant hirudin (anticoagulant action, similar to antithrombin III - the thrombin inhibitor)  For HIT complicated by thrombosis, preventing new thromboses  Not for renal failure patients  Argatroban  Is a direct thrombin inhibitor  Metabolized in the liver  Activity monitored by APTT  Good for renal failure patients  Warfarin — when 1) patient stably anticoagulated with a thrombin-specific inhibitor 2) Plt > 150,000/microL
  23. 23. Challenges in bridging to long term anticoagulation  The combination of argatroban and warfarin may raise the INR > 5.0 without a significant increased risk of bleeding complications.  Measure the chromogenic factor X level  A level < 40-45% typically indicates that the INR will be therapeutic (2-3) when the argatroban is discontinued.
  24. 24. HIT I  Non-immune mechanism, appears to be due to a direct effect of heparin on platelet activation  1-4 days after heparin is started  Platelets in the 100.000/mm3 range  No thrombotic events  No hemorrhage  Management : observation
  25. 25. HIT I vs HIT II
  26. 26. Thrombotic thrombocytopenic purpura- hemolytic uremic syndrome (TTP-HUS)  Thrombocytopenia  Microangiopathic hemolytic anemia  Neurologic symptoms and signs  Renal function abnormalities  +/- Fever  TTP-HUS is associated with thrombi composed primarily of platelets in affected organs
  27. 27. Etiology TTP  ADAMTS13 deficiency (vWf-cleaving protease) —leads sequentially to the accumulation of unusual large vWf multimers, platelet aggregation, and the platelet clumping  Genetic  Acquired: DIC, HSCT, chemotherapy, severe sepsis, SLE, leukemia, acute inflammatory states, cirrhosis, uremia, drugs (ticlopidine, clopidogrel, quinine)
  28. 28. Etiology HUS  Enterohemorrhagic E coli  Shiga toxin binds and activates endothelial cells and platelets and induces formation of intra-renal thrombi Clinic:  Children  Bloody diarrhea  Fever
  29. 29. Diagnosis TTP-HUS  Peripheral smear: ++ Schystocytes  Negative Coombs test  Normal PT, PTT, fibrinogen  Hemolysis : LDH increased (tissue ischemia + hemolysis), indirect bilirubin increased, decreased haptoglobin  Increased creatinine  Biopsy: arterioles filled with hyaline thrombi (DDx: vasculitis, DIC, HELLP, malignant HTN)
  30. 30. Treatment TTP-HUS 1. Plasma exchange Exceptions:  Postdiarrheal HUS in children  Cancer chemotherapy or transplantation  Severe acute renal failure- cause fluid overload 2. Glucocorticoids: severe deficiency of ADAMTS13 Platelet transfusions are contraindicated
  31. 31. Immune thrombocytopenic purpura (ITP)  Dg of exclusion  ITP is related to a combination of  increased platelet destruction along with  inhibition of megakaryocyte platelet production via the production of specific IgG autoantibodies directed against platelet membrane GP (GPIIb/IIIa)
  32. 32. Diagnosis ITP  CBC : ITP+AIHA = Evans Sdr  Peripheral smear: large platelets  Bone marrow aspirate >60 yo to r/o MDS  Antiplatelet antibody testing –not recommended by the ASH  Platelets have HLA A, B-testing for anti-HLA ab to match platelets  Consider ANA, viral serologies, H pylory Ab
  33. 33. Treatment ITP  Initial :  Steroids: PDN/ methylprednisolone (bleeding)  IVIG  WinRho (AntiRh-D) in Rh positive pt; ab coated RBC overwhelm Macrophages Fc receptor  Refractory  Splenectomy  Rituximab (anti-CD20)  Azathioprine, Cyclophosphamide  Thrombopoiesis stimulant: Eltrombopag
  34. 34. References  www.uptodate.com  John Hopkins IM board review  PG MGH handbook
  35. 35. Thank you! ALYSA & ANA

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