1 / 93

Heparin Induced Thrombocytopenia

Heparin Induced Thrombocytopenia. Jennifer Howard D.O. June 4, 2002. Case.

rosalyn-sweet
Download Presentation

Heparin Induced Thrombocytopenia

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Heparin Induced Thrombocytopenia Jennifer Howard D.O. June 4, 2002

  2. Case • 68 yo WF with hx of HTN and DM presents to ER after a fall. She is found to have a hip fracture and the plan is to go to surgery after medical clearance. Prophylactic SQ unfractionated heparin is started and continued for 3d while pt is cleared for surgery.

  3. Case • After surgery the heparin is restarted and 2 days later the patient is moved to rehab. After transfer the patient complains of redness and swelling of arm near site of subclavian TLC. Labs reveal mild leukocytosis and Platelets of 85,000. Doppler US shows an acute DVT of the arm.

  4. Case • Med list: Insulin SS, Demerol, HCTZ, Captopril, Heparin SQ, and Tylenol • Questions: • Why does she have thrombocytopenia? • Why does she have a DVT? • Is this HIT? • How do we treat her now?

  5. Introduction • Thrombocytopenia is a well-recognized complication of heparin treatment • Two types of heparin induced thrombocytopenia

  6. Type 1 HIT • Less serious • Less severe decrease in platelet count • Occurs 1-2 days after heparin initiation • Usually returns to baseline with continued heparin administration • No clinical consequence • Non-immune, due to a direct effect of heparin on platelet activation

  7. Type 2 HIT • More serious • Immune-mediated disorder with formation of antibodies against heparin-PF4 complex • Aka heparin associated thrombocytopenia and white clot syndrome • “white clot” is a platelet rich arterial thrombosis

  8. HIT- Pathophysiology • Antigen of HIT • Tetrameric glycoprotein found in platelet alpha granules • Platelet Factor 4 (PF4) • PF4 is positively charged and binds negatively charged sulfated polysaccharide chains of heparin • A conformational change occurs producing an immunoglobulin response to the altered PF4 in some pts

  9. HIT- Pathophysiology • PF4, heparin, and IgG antibodies form multimolecular complexes and bind to the platelet surface • Platelet activation occurs • Releases more PF4 • Leads to thrombin generation and procoagulant effect

  10. HIT- Pathophysiology • HIT antibodies also react with the heparin-PF4 complex on endothelial cells and monocytes • Leads to tissue factor expression • Procoagulant response

  11. HIT- Pathophysiology • Activated platelets aggregate and are removed prematurely from the circulation, causing thrombocytopenia • HIT is uniquely assoc with platelet activation • May explain assoc with thrombosis rather than bleeding

  12. HIT- Pathophysiology • LMWH is smaller in size than UFH but can still complex with PF4 • HIT may recur or persist if LMWH is used to treat HIT triggered by UFH

  13. HIT-Incidence and Frequency • Frequency of HIT varies from 1-5% of pts receiving UFH • Highest frequency 3-5% reported in post op orthopedic pts who received prophylactic UFH for 10-14days • <1% in medical pts- prophylactic or therapeutic doses

  14. HIT-Incidence and Frequency • Highest frequency of HIT Ab in cardiac surgical pts but lower risk of HIT • Risk of LMWH-induced HIT very low in medical pts but up to .5% in ortho pts receiving LMWH for 10-14d

  15. HIT-Incidence and Frequency • 10-20% of pts receiving UFH have 50% drop in platelets or drop to below normal range • In one study of 665 hip surgery pts receiving heparin prophylaxis • UFH- 7.8% had anti-heparin Ab, 2.7% developed HIT • LMWH- 2.2% had anti-heparin Ab, 0% developed HIT

  16. HIT-Incidence and Frequency • Most pts who develop HIT have received IV or SQ heparin • Cases reported from hepflush or use of heparin-coated catheter

  17. Thrombocytopenia • Normal platelet counts in adults 150,000-450,000 • Mean values: 237,000 in men 266,000 in women • Definition: platelet count <150,000 per microliter • 2.5% of the normal population have platelets < 150,000

  18. Thrombocytopenia • Surgical bleeding due solely to thrombocytopenia does not occur until plts < 50,000 • Clinical or spontaneous bleeding does not occur until plts <10,000-20,000

  19. Thrombocytopenia- Clinical Presentation • Most cases of thrombocytopenia are asymptomatic • Most common symptomatic presentation is bleeding • Mucosal- epistaxis, gingival bleeding • Cutaneous- petechiae, superficial ecchymoses

  20. Thrombocytopenia- Clinical Presentation • Bleeding with platelet abnormalities occurs immediately after vascular trauma • Rarely have delayed bleeding in contrast to coagulation disorders • CNS bleeding is uncommon but it is the most common cause of death due to thrombocytopenia

  21. Thrombocytopenia • Platelets are produced in the bone marrow from megakaryocytes • The megakaryocyte produces plts by cytoplasmic shedding directly into marrow sinusoids • Normal platelet production is 35,000-50,000 per mcL per day- can be increased 8x if increased demand

  22. Thrombocytopenia • Once in circulation, plts survive 8-10 days • Plts are removed from circulation by the monocyte-macrophage system • One third of the platelet mass is in the spleen is equilibrium with the circulating pool

  23. Thrombocytopenia- Mechanisms • 4 mechanisms explain reduced platelets • 1- decreased production* • 2- increased destruction* • 3- spurious • 4- dilutional or distributional

  24. Thrombocytopenia- Decreased Production • Decreased production by bone marrow occurs when the marrow is suppressed or damaged • After viral infection • After chemotherapy or radiation • Congenital or acquired BM aplasia/ hypoplasia • Direct alcohol toxicity • Vitamin B12/ folate deficiency

  25. Thrombocytopenia- Increased Destruction • Seen in may conditions • Certain viral infections like mono and CMV • Physical destruction during CP bypass • ITP • DIC • HELLP • Drugs • TTP-HUS

  26. Thrombocytopenia- Dilutional/Distributional • After massive blood loss and transfusions with PRBC’s • Splenic sequestration can increase from Nl 30% to 90% • Seen in extreme splenomegally • Platelet mass and survival remain normal

  27. Thrombocytopenia- Spurious • If anticoagulation of the blood sample is inadequate platelets clump and are counted as leukocytes • .1% of normal people have EDTA-dependent agglutinins which lead to clumping and spurious leukocytosis

  28. Thrombocytopenia- Initial Approach • If the platelet count does not make sense, repeat it • History- recent viral infection, alcoholism, pregnancy, etc • Bleeding history- past bleeding problems, iron def anemia, bleeding after dental work, menses, etc • Drug ingestion- heparin, valproic acid, gold salts, bactrim, quinine, etc

  29. Thrombocytopenia- Physical Exam • Check ocular fundus for bleeding • Lymphadenopathy • Hepatosplenomegaly • Stool for occult blood • Skin- petechiae in dependent areas

  30. Thrombocytopenia- CBC + Peripheral Smear • Need to do this fairly quickly since TTP and acute leukemia need quick treatment • Pseudothrombocytopenia can be confirmed by presence of clumps on smear

  31. Thrombocytopenia- Peripheral Smear • Abnormal platelet morphology • Small number of congenital disorders that can be diagnosed by abnormal morphology • May- Hegglin anomaly • Bernard-Soulier Syndrome • Alport Syndrome • Wiskott-Aldrich syndrome

  32. Thrombocytopenia- Decreased Production • Circulating blasts-> acute leukemia • Leukoerythroblastic picture-> BM invasion by tumor, fibrosis, granulomata • Other cytopenias-> myelodysplasia • Normal size or small platelet-> absence of effective BM response to the increased need

  33. Thrombocytopenia- Increased Destruction • Microangiopathic picture with fragmented RBC’c, hemolytic anemia-> DIC, TTP-HUS • Large platelets-> young platelets that are hemostatically active without bleeding • Associated autoimmune disease (SLE)

  34. Thrombocytopenia-BM Biopsy • Indicated in virtually all pts with unexplained thrombocytopenia • May exclude healthy people under 60 • Normal or increased megakaryocytes-> increased peripheral destruction • Absent or decreased megakaryocytes with hypocellularity-> decreased production

  35. Thrombocytopenia- BM Biopsy • Hypercellular marrow- myelodysplasia or B12/folate def • Granulomata, fibrosis or malignant cells-> marrow invasion

  36. Thrombocytopenia • Incidental Thrombocytopenia of Pregnancy • ITP-> exclude all other causes

  37. HIT- Clinical Manifestations • HIT is a clinicopathologic syndrome • Clinical criterion: thrombocytopenia • Pathologic criterion: HIT antibodies

  38. Clinical Manifestations- Thrombocytopenia • Thrombocytopenia is usually mild-mod • Often complicated by thrombosis • Platelet count begins to fall 5-10 days after receiving heparin • Median platelet count falls to 60,000/mcL • 60% moderate 30,000-100,000 • 20% severe <30,000 • 20% mild >100,000 • Typical drug-induced thrombocytopenia <20,000

  39. Clinical Manifestations- Thrombosis In >50% thrombosis occurs new, recurrent or progressive Especially pts with severe thrombocytopenia Thrombosis can be venous or arterial Highest occurrence: DVT 50%, PE 25% Other reactions: skin, transient global amnesia, acute systemic reaction

More Related