Flash Player 9 (or above) is needed to view presentations.
We have detected that you do not have it on your computer. To install it, go here.

Like this presentation? Why not share!

Like this? Share it with your network


Hematologic/Coagulation Cases in Critical Care

Uploaded on


  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Be the first to comment
No Downloads


Total Views
On Slideshare
From Embeds
Number of Embeds



Embeds 1 1

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

    No notes for slide


  • 1. Hematologic/Coagulation Cases in Critical Care Alice Ma, M.D. University of North Carolina-Chapel Hill Division of Hematology
  • 2. Case 1
    • A 21 y.o. UNC student presented to the coagulation clinic from the plastic surgery clinic. He had undergone nipple piercing 11 days prior and had prolonged bleeding, requiring 2 trips to the emergency room, gelfoam application, pressure dressing, stitching, re-stitching. He was still actively bleeding.
    • PMHx was notable for tongue laceration at age 7 following a fall, with persistent bleeding. Thumb injury with persistent bleeding, ganglion cyst removal without abnormal bleeding.
  • 3. Case 1
    • Family History - mother is on iron for unknown reasons. Maternal grandmother may have abnormal bleeding (pt unsure) Sister alive and well without abnormal bleeding.
    • Meds - none
    • SHx - senior at UNC, occasional alcohol, no tobacco or drugs
    • PEx - actively bleeding left nipple. No bruises or petechiae.
  • 4. Case 1- Initial Laboratory Studies
    • PT 13.9 sec (11-14)
    • aPTT 52.2 sec (22-32)
  • 5. Case 1 - questions
    • Question 1: How do we evaluate patients with an abnormal aPTT?
    • Question 2: What does the patient have?
    • Question 3: How should the patient be treated?
  • 6. Obligatory Confusing Coag Cascade
  • 7. Coagulation made easy The PTT Pathway The PT Pathway
  • 8. Coagulation made easy X The PTT Pathway The PT Pathway
  • 9. Coagulation made easy V X The PTT Pathway The PT Pathway
  • 10. Coagulation made easy V X The PTT Pathway The PT Pathway Prothrombin Thrombin
  • 11. Coagulation made easy V X The PTT Pathway The PT Pathway Prothrombin Thrombin Fibrinogen Fibrin
  • 12. Coagulation made easy - the PT 7 V X Prothrombin Thrombin Fibrinogen Fibrin
  • 13. Coagulation made easy - the aPTT V X XII XI IX VIII Prothrombin Thrombin Fibrinogen Fibrin
  • 14. Coagulation made easy - the aPTT T N E T V X E Prothrombin Thrombin Fibrinogen Fibrin
  • 15. Coagulation made easy - the aPTT T welve N ine E ight T en V X E leven Prothrombin Thrombin Fibrinogen Fibrin
  • 16.
    • Deficiencies of factor XI, IX, VIII, VII. X, V, prothrombin and fibrinogen are clinically significant.
    • Inhibitors of these factors are clinically significant.
    • Deficiency of Factor XII, and the presence of the lupus anticoagulant are not clinically significant.
    XII XI IX X VIII VII Thrombin V What matters clinically Fibrinogen Fibrin
  • 17. Coagulation Made Easy- The Mixing Study
    • Useful to differentiate etiologies of prolonged clotting in a coagulation assay.
    • Patient’s plasma is mixed 50:50 with normal plasma. Coagulation assay is repeated.
    • If “substantial” correction is noted after mix, suspect clotting factor deficiency .
    • If no or minimal correction seen, suspect inhibitor .
  • 18. Case 1 - More Laboratory Data
    • aPTT - 52.2 sec (22-32)
    • aPTT mix - 31.5 sec
  • 19. Case 1 - More Laboratory Data
    • aPTT - 52.2 sec (22-32)
    • aPTT mix - 31.5 sec
    • Interpretation: Factor Deficiency
  • 20. Case 1 - Which Factor(s) are deficient? T welve N ine E ight T en V X E leven Prothrombin Thrombin Fibrinogen Fibrin
  • 21. Case 1 - More Laboratory Data Question 2: What does the patient have? Factor II 104% Factor V 111% Factor VIII 128% Factor IX 2% Factor X 129% Factor XI 78%
  • 22. Hemophilia
    • X-linked recessive disorder
    • Hemophilia A - deficiency of Factor VIII
    • Hemophilia B - deficiency of Factor IX
    • Incidence 1/5000 live male births
    • Estimated 20,000 cases in US; 1,000 in NC
    • Racial groups affected with similar frequency
  • 23. Clinical Classification of Hemophilia Severe < 1% Moderate 1% - 5% Mild 5% - 25% Severe hemarthrosis Spontaneous bleeding Serious bleeding after minor trauma Bleeding after surgery or trauma Moderate bleeding after trauma or surgery Type FVIII/IX activity Clinical picture Subclinical 25% - 50%
  • 24. Hemophilia Treatment
    • Replace Deficient Factor
    • Many Products: Two general categories:
      • Plasma derived
        • Virally inactivated
        • Generally reserved for individuals who are HIV/HepC positive
      • Recombinant
        • More expensive
        • Should be product of choice for all children and previously untreated patients
    • Inhibit Fibrinolysis - in mucosal bleeding
  • 25. Hemophilia Treatment
    • Clotting factor is dosed in UNITS
    • One Unit = amount of factor present in 1 ml of normal plasma
    • Replacement Factor Dosing is based on 3 variables
      • Volume of distribution (extravascula/intravascular)
      • Half-life
      • Level of factor required for hemostasis
  • 26. Hemophilia Treatment Site of Bleeding Optimal Factor Level Duration in days Joint or muscle 30-50 1-2 GI tract 40-60 7-10 Oral, nasal, GU mucosa 30-50 Until healing CNS 80-100 10-21 Retroperitoneal 80-100 7-14 Surgery/Trauma 80-100 7-21
  • 27. Case 1 - Followup
    • The patient was given a bolus dose of 4,000 units of BeneFIX (recombinant Factor IX) calculated to raise his Factor IX level to 50%. Pressure was re-applied, and the bleeding stopped. This dose of factor cost approximately $6,000. The patient is uninsured.
    • The patient was instructed to seek care at the regional comprehensive hemophilia center after graduation.
  • 28. Teaching Points
    • A prolonged PTT should be evaluated first by mixing study, then with factor levels, if appropriate.
    • Hemophilia can be undiagnosed until adulthood, especially if mild or moderate.
    • Treating hemophilia is expensive and complicated, and patients should be followed in a comprehensive hemophilia center.
  • 29. Case 2
    • A 33 y.o. man presented with post-operative bleeding after a tonsillectomy.
    • 10/15/01 – Hb/Hct = 15.3/42.7.
      • PT/aPTT = 13/35.6 (22-33.4)
    • 10/17/01 – Tonsillectomy.
    • 10/17-10/24, pt took ibuprofen for pain
    • 10/24 early am – Pt awoke with severe bleeding
      • Hb/Hct in ER 14.1/38
  • 30. Case 2
    • Bleeding did not stop with ER cauterization.
    • Pt given platelets, FFP, then taken to OR
    • Notice made of persistent venous oozing and bleeding. DDAVP given
    • 10/25 – Pt had persistent post-op bleeding
    • H/H eventually reached 9.1/25
  • 31. Case 2
    • Bleeding History:
      • Lifelong nosebleeds
      • Gum bleeding with brushing teeth
      • Prolonged bleeding with nicks
      • Bleeding with multiple tooth extractions (characterized as delayed)
      • appy at age 19, wound dehisced and bled
    • FHx - sister with easy bruising and abnormal menstrual bleeding. Mother had hysterectomy in early 30’s.
  • 32. Case 2 - Questions
    • Question #1 - What is a reasonable screening evaluation for patients pre-operatively?
    • Question #2 - What is a reasonable screening evaluation for patients with a positive bleeding history?
    • Question #3 - What does the patient have?
    • Question #4 - How should the patient be treated prior to future surgical interventions?
  • 33. Case 2
    • PT - 12.9 seconds. (11-14)
    • aPTT - 33.9 seconds (22-33.4).
    • Platelet function screen.
      • col/epi closure time >300 sec (84-178)
      • col/ADP closure time 136 sec (60-107)
  • 34. The platelet function screen
    • An in vitro method to test primary hemostasis
    • Measures the length of time for whole citrated blood taken up by microcapillary membranes permeated with either collagen + epinephrine or collagen + ADP to close off the microcapillaries.
    • Designed to replace the bleeding time
  • 35. The platelet function screen
  • 36. The platelet function screen
    • Prolonged in cases of platelet dysfunction (acquired or congenital) or von Willebrand’s disease.
    • If hematocrit is <30 or if platelet count is <100, this test will be abnormal.
    • Assay must be run within 4 hours of sample draw.
    • Sample is run on Whole Blood--NOT PLASMA!!
  • 37. Case 2 - More laboratory data
    • vWF antigen - 58%
    • vWF activity - 50%
    • Platelet aggregation studies: abnormal aggregation in response to epinephrine, ADP, arachidonic acid.
  • 38. Case 2 Question #3: How should the patient be treated prior to future invasive procedures? Pre-DDAVP Post-DDAVP Col/epi >300 sec 133 sec Col/ADP 98 sec 56 sec vWF antigen 67% 151% vWF activity 78% 219%
  • 39. Case 2
    • The patient was told he had mild Type I von Willebrand’s disease, coupled with a mild platelet dysfunction. He subsequently suffered a left ACL rupture and underwent surgical repair under coverage with DDAVP.
    • He did well and had no abnormal bleeding.
  • 40. Teaching Points
    • Take a bleeding history. Then, write it down.
    • Not all bleeding diatheses show up with a PT/PTT.
    • Defects in primary hemostasis cause mucocutaneous bleeding (“Oozing and Bruising”) and are best screened for by using the platelet function screen (PFA-100).
    • DDAVP can improve primary hemostasis.
  • 41. Bleeding History
        • Nosebleeds
        • Gum bleeding
        • Bleeding with (wisdom) tooth extraction
        • Easy bruisability
        • Bleeding with surgeries (including circumcision)
          • Include timing of bleeding
        • Menstrual bleeding
        • Transfusion requirements
        • Family history of bleeding
          • Hysterectomies at an early age
          • Bleeding with surgeries
  • 42. Case 3
    • A 72 y.o. man suffered complications of an MVA with multiple fractures and splenic rupture 7 days prior. He is now thought to be septic and all wounds are bleeding.
    • Labs show H/H 7/21, Plts 14, PT 33, PTT 60 Fibrinogen 81
    • After transfusion of 4 units PRBC, H/H only 8/23
  • 43. Case 3 - Questions
    • Q1. What blood products should be given to the patient?
    • Q2. What are the indications for use of Novo-Seven in the bleeding surgical patient?
  • 44. What blood products to give?
    • H/H 7/21, Plts 14, PT 33, PTT 60 Fibrinogen 81
    • Platelets - With active hemorrhage, try to keep platelets > 50. If no bleeding, keep platelets >10
    • Cryoprecipitate - With active bleeding, keep fibrinogen >100. Cryo also contains FVIII, VWF, FXIII
    • RBCs - With active bleeding and thrombocytopenia, plts will work better if Hgb >10
  • 45. Review Cascade model of hemostasis Xa generation Thrombin Generation Intrinsic pathway XI, IX, VIII Extrinsic pathway TF, VII
  • 46. A Cell-Based Model of Hemostasis
    • Initiation
    • Amplification
    • Propagation
  • 47. Initiation
  • 48. Amplification
  • 49. Propagation
  • 50. Hemostasis
  • 51. Hemophilia is a Defect in Plateetl Surface Thrombin Generation
  • 52. NovoSeven can Ameliorate the Defect in Hemophilia
  • 53. NovoSeven Augments Thrombin Generation on the Platelet Surface in Non-Hemophilics
  • 54. NovoSeven in Surgery/Trauma
    • This is an Off-Label Use
    • Pts are at significant risk for thrombosis, especially if they have activated platelets in circulation (ie vasculopaths, DIC)
    • Remember that rVIIa requires platelets, Factor X, prothrombin, and fibrinogen to work, so
    • Fix the Plts, PT, PTT, Fibrinogen.
    • If pt still bleeding, can then give rVIIa
  • 55. Case 4
    • A patient presents with a perforated diverticular abscess. He has alcoholic cirrhosis and poor nutrition.
    • His PT and PTT are prolonged at baseline to 18 and 48 sec, respectively. DIC screen shows fibrinogen of 300, Ddimers of 800
    • How can we use factor levels to determine the cause of his coagulopathy?
  • 56. Case 4 Vitamin K Deficiency Liver Disease DIC Factor V    Factor VII    Factor VIII    / 
  • 57. Case 5
    • A 65 y.o. female smoker with a h/o peripheral vascular disease presented to the ER with unstable angina. She was admitted to the hospital and placed on heparin. Platelet count on admission was 450. Cardiac catheterization showed severe 3-vessel coronary disease, and the patient was scheduled for CABG which occurred on hospital day #7. Pre-op platelet count was 200. Post-op platelet count was 90.
  • 58. Case 5
    • On hospital day #12, the patient developed acute left leg swelling and a DVT was diagnosed by ultrasound. Platelet count was 150. The patient was started on IV heparin. The next day, she developed a pulseless left leg and had a platelet count of 30. While in vascular radiology, he developed acute chest pain and suffered a cardiac arrest and subsequently died. Autopsy showed occlusion of all of her bypass grafts
  • 59. HIT
    • Seen in 1-3% of patients treated with heparin
    • Usually, 7-10 d after heparin started, platelets fall by at least 1/3 to 1/2.
      • Patients do not have to be thrombocytopenic .
      • Can occur earlier in patients who have been previously exposed to heparin, even as SQ injections.
    • Caused by antibodies against the complex of heparin and PF4. These antibodies activate platelets.
    • Can lead, paradoxically, to THROMBOSIS , in up to half of patients.
    • More common in patients with vascular disease
  • 60. Alternate Presentations of HIT/T
    • Small drop in platelet count (especially with skin necrosis)
    • Earlier onset thrombocytopenia with heparin re-exposure
    • Delayed-onset thrombocytopenia/ thrombosis after stopping heparin
    • Thrombosis after heparin exposure
  • 61. HIT/T treatment
    • Stop heparin
    • Stop heparin
    • Use a different anticoagulant
      • Lepirudin
      • Argatroban
      • Bivalirudin (off label)
      • Fondaparinux (off-label)
  • 62. HIT Testing Test Advantages Disadvantages HIPA Specificity: high Sensitivity: low Rapid turn around time Technique-dependent ELISA Sensitivity: high Specificity: low (false-positives Technically easy high for some populations) Poor concordance with SRA There is no Gold Standard in diagnostic testing; HIT is a clinical diagnosis Pts Must Be off heparin for 16 hours prior to testing
  • 63. Lepirudin
    • Recombinant protein, irreversibly binds to and inactivates thrombin
    • Associated with increased bleeding, compared to heparin.
    • Short t 1/2 .
    • Renally excreted.
    • Antibody formation is common
      • decrease clearance and potentiate anticoagulation effect.
      • Allergic reactions may occur
    • Monitor by using aPTT (aim for 50-70 sec)
  • 64. Argatroban
    • Synthetic direct thrombin inhibitor
    • Reversibly binds to thrombin’s catalytic site
    • Associated with increased bleeding compared to heparin
    • Short t 1/2 - must give as continuous infusion - no loading dose
    • Dose is 0.2 mcg/kg/min (maximum dose is 10 mcg/kg/min)
    • Monitor using the aPTT (aim for aPTT 50-80)
    • Hepatically cleared - reduce dose by 75% in liver failure.
    • Prolongs the PT.
  • 65. Fondaparinux
    • Derived from AT-binding moiety of heparin.
    • Leads to indirect inhibition of Xa.
    • Once daily SQ therapy
    • Renally cleared
    • Approved for treatment of VTE and prophylaxis of patients at high risk for VTE (hip, knee surgery, abdominal surgery)
    • Not approved for use in HIT
  • 66. Case 6
    • A 72 y.o. woman requires red cell transfusion for symptomatic anemia. Red cells are delivered to the bedside. The patient verbally confirms her name and date of birth, which correlate with the label on the red cell bag. Which of the following is the most appropriate course of action to take at this time?
  • 67. Case 6
    • Proceed with the transfusion.
    • Have another health care professional witness the patient’s confirmation of her ID, then proceed with the transfusion.
    • Check the patient’s wrist ID band against the red cell bag tag, along with another health care professional witness, then proceed with the transfusion.
    • Check the patient’s wrist ID band against the red cell bag tag, along with another health care professional witness, confirm that the consent for transfusion form has been signed, then proceed with the transfusion.
  • 68. Case 7
    • A patient in the SICU is in the process of receiving a transfusion of platelets for a platelet count of 8. Midway through the transfusion, the patient’s temperature rises from a baseline of 36.8 to 38. The blood pressure is stable, and the pulse has risen from 88 to 102. There are no hives, stridor, back pain, or rash. The patient is already on broad spectrum antibiotics. What is the most apropriate course of action to take at this time?
  • 69. Case 7
    • Draw blood cultures, administer acetominophen, then proceed with the transfusion before the unit of platelets expire.
    • Draw blood cultures, administer acetominophen, then proceed with the transfusion when the temperature reaches baseline.
    • Draw blood cultures, change antibiotics, administer acetominophen, then proceed with the transfusion when the temperature reaches baseline.
    • Stop transfusion, draw workup for possible transfusion reaction, send workup and remainder of platelets to blood bank, and do not give further blood products until workup is negative.
  • 70. Case 8
    • A patient with aplastic anemia is scheduled to undergo breast biopsy in the morning. Her platelet count is 4. What is the most appropriate course of action at this point?
  • 71. Case 8
    • Order 2 doses of platelets for transfusion.
    • Order 2 doses of platelets for transfusion, then check platelet count in the morning before procedure.
    • Order 1 dose of platelets for transfusion , then check platelet count in the morning before procedure.
    • Order 1 dose of platelets for transfusion , then check platelet count before ordering another dose of platelets.