Hematology Emergencies: Problems with Platelets

Transcription

1 Hematology Emergencies: Problems with Platelets Christian Cable, MD, FACP Associate Professor of Medicine Division of Hematology & Oncology Texas A&M HSC College of Medicine Scott & White Healthcare Fundamentals of Hospital Medicine Temple, TX 1/11/2013

2 Learning Objectives Recognize three distinct, scary inpatient low platelet problems Utilize relevant pathophysiology to distinguish these entities Enable participants to initiate appropriate diagnostic and therapeutic maneuvers

3 Disclosures I love the blood I am especially fond of platelets I am not a vampire I only take money from Scott & White, American College of Physicians, and my wife

4 The Call...

5

6 What could go wrong?

7 Figure 1. Large ecchymotic area over the thigh following minor trauma Lazarchick, J. ASH Image Bank 2001;2001: Copyright 2001 American Society of Hematology. Copyright restrictions may apply.

8 Platelet Problems Platelets in health Why we bleed ITP TTP HIT Conclusions

9 Platelet Problems Platelets in health Why we bleed ITP TTP HIT Conclusions

10 Figure 1. Granulocytes circulating in the blood of a patient with a normal peripheral smear Maslak, P. ASH Image Bank 2008;2008: Copyright 2008 American Society of Hematology. Copyright restrictions may apply.

11 What is that? dust on the slide Early 1900 s - - inert plug Currently - - inert but poised *metabolically active*

12 Figure 1. The granular appearance of the platelets helps to distinguish them from artifact in the peripheral smear Maslak, P. ASH Image Bank 2005;2005: Copyright 2005 American Society of Hematology. Copyright restrictions may apply.

13 Figure 1. Damage to the vascular endothelium results in recruitment of platelets which aggregate at the site, forming the primary hemostatic plug Maslak, P. ASH Image Bank 2008;2008: Copyright 2008 American Society of Hematology. Copyright restrictions may apply.

14 Figure 2. Through the processes of adhesion, aggregation, and secretion, platelets successfully coalesce to complete the formation of the primary hemostatic plug Maslak, P. ASH Image Bank 2008;2008: Copyright 2008 American Society of Hematology. Copyright restrictions may apply.

15 Figure 1. Secondary hemostasis involves the deposition of fibrin which results in fine clot formation Maslak, P. ASH Image Bank 2008;2008: Copyright 2008 American Society of Hematology. Copyright restrictions may apply.

16 Hoffman Hematology, 5 th ed. Fig 114-7

17 Hoffman Hematology, 5 th ed. Fig 115-1

18 UpToDate, 17.1

19 Hoffman Hematology, 5 th ed. Fig 116-2

20 Nachman, NEJM Sept 18, 2008

21 Platelets...

22 ... plug the holes.

23 Platelet Problems Platelets in health Why we bleed ITP TTP HIT Conclusions

24 Nachman, NEJM Sept 18, 2008

25 Nachman, NEJM Sept 18, 2008

26 How low can you go?

27 Spontaneous Bleeding... <10

28 Platelet Problems Platelets in health Why we bleed ITP TTP HIT Conclusions

29 CC: 39 weeks pregnant, low platelets 26 y.o. woman Modest bruising, close to delivery CBC...

30

31 Figure 2. Peripheral smear in a patient with ITP showing an almost total absence of platelets Lazarchick, J. ASH Image Bank 2001;2001: Copyright 2001 American Society of Hematology. Copyright restrictions may apply.

32 Immune TP F ab F Cγ

33 Bromberg, NEJM Oct 19, 2006

34 When giants roamed the halls...

35 ITP treatment Decrease antibody production Block antibody coated platelets from being destroyed in spleen Increase platelet production Transfusion Stimulate thrombopoeisis

36 ITP treatment Steroids IV immune globulin Splenectomy Platelet transfusions if bleeding New agents to increase platelet production

37

38 Success?

39 Platelet Problems Introduction Platelets in health Why we bleed ITP TTP HIT Conclusions

40 CC: Seizure, low platelets 39 y.o. AA woman with known seizures To ER for recurrent seizures, bruising on exam CBC...

41

42 Figure 1. Peripheral smear showing microangiopathic hemolytic features with numerous RBC fragments (helmet cells/schistocytes) Lazarchick, J. ASH Image Bank 2001;2001: Copyright 2001 American Society of Hematology. Copyright restrictions may apply.

43 Thrombotic TP Microangiopathic hemolytic anemia + thromobocytopenia is a very short list. The list does NOT include ITP. TTP is caused by an antibody directed against a protease that cleaves the vonwillebrand molecule. Longer vwf is more sticky and causes platelets to stick in small vessels. This causes multi-organ ischemia and the shearing of red cells.

44 UpToDate, 17.1

45 Harrison s, 17 th ed. Fig 109-4

46 ADAMTS-13 protease F ab F Cγ

47

48 CONTRAindications to Transfusion Platelets - - if the platelets are on fire, don t add more TTP HIT

49

50 x 48 treatments

51 Success?

52 Platelet Problems Platelets in health Why we bleed ITP TTP HIT Conclusions

53 NEJM 355;8 (809-17) August 24, 2006

54 In the Water?

55 HIT - - working diagnosis A decrease in platelet count (<150K or >50%) associated with heparin exposure in a typical time course that has a high risk of thrombotic (not bleeding) complications which requires alternative anticoagulation upon diagnosis.

56 Heparin in the Hospital Orthopedic Surgery Cardiac Surgery General Medical Patients Acute Coronary Syndrome - - PCI Acute Hemodialysis Kids Pregnancy Chronic Hemodialysis

57 Types of Heparin Unfractionated (15kDa~45 saccharide) LMWH (5kDa ~ 15 saccharide) Super LMWH (1.7 kda pentasaccharide) Interact with AT and Xa to reverse coagulation (Super LMWH just Xa)

58 How Heparin Works WARNING - - clotting cascade Tissue Factor F VII

59 WARNING - - clotting cascade F X F VIIa

60 WARNING - - clotting cascade F Xa Prothrombin

61 WARNING - - clotting cascade Thrombin

62 WARNING - - clotting cascade Thrombin Fibrinogen Fibrin

63 WARNING - - clotting cascade Anti-thrombin Thrombin Fibrinogen Fibrin

64 Heparin WARNING - - clotting cascade Anti-thrombin Thrombin Fibrinogen Fibrin

65 Heparin WARNING - - clotting cascade Anti-thrombin Thrombin Fibrinogen Fibrin

66 Heparin WARNING - - clotting cascade Anti-thrombin Thrombin Fibrinogen Fibrin

67 Heparin Pathophysiology Platelet PF4

68 Heparin Pathophysiology Platelet Y PF4 Y

69 Platelets coated by antibodies Aggregate (like a Coombs test) Cleared by spleen (thrombocytopenia) Activated (thrombosis) Platelet PF4 Y

70 Diagnosis Timing Thrombocytopenia Thrombosis Alternate Causes

71 Timing In a patient exposed to heparin for the first time in 100 days, HIT begins after 4-14 days of heparin use A rapid fall in platelets soon after heparin is unlikely to be HIT

72 Thrombocytopenia <150K 50% fall from peak It is uncommon for HIT to cause single digit thrombocytopenia

73 Thrombosis Even after stopping heparin 50% of patients with HIT will clot within the first 30 days Odds ratio for clot w/ HIT = 37 Venous > Arterial DVT/PE most common Weird clots - - HIT more likely

74 Management 2 Do 2 Don t 2 Tests

75 DO Stop ALL heparin - - even flushes Start alternative anticoagulation - - before confirmatory tests return

76 Alternative Anticoagulation Direct Thrombin Inhibitors Lepirudin Not good in kidney dysfunction Argatroban Really messes up the INR Fondaparinux to temporize?

77 DON T Use coumadin too soon - - wait for full platelet recovery, must have sufficient overlap Transfuse platelets - - along with TTP this is a contraindicated condition for platelet transfusions!

78 2 Tests ELISA for antibody to PF4 (usually a sendout, but the most helpful confirmatory test) Bilateral LE Doppler Venous Ultrasound (the presence of thrombosis greatly strengthens your case)

79 Platelet Problems Introduction Platelets in health Why we bleed ITP TTP Conclusions

80 The Call...

81

82

83

84 Diagnosis? ITP Should not have red cell changes Can give platelets Plasma exchange not helpful HIT Needs the H! No platelets TTP Schistocytes No platelets Needs plasma exchange

85 Success?

86

87 Platelet Problems Platelets in health Why we bleed ITP TTP HIT Conclusions

88