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Hematologic/Coagulation Cases in Critical Care Alice Ma, M.D. University of North Carolina-Chapel Hill Division of Hematology.

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Presentation on theme: "Hematologic/Coagulation Cases in Critical Care Alice Ma, M.D. University of North Carolina-Chapel Hill Division of Hematology."— Presentation transcript:

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.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.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.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 - noneMeds - none SHx - senior at UNC, occasional alcohol, no tobacco or drugsSHx - senior at UNC, occasional alcohol, no tobacco or drugs PEx - actively bleeding left nipple. No bruises or petechiae.PEx - actively bleeding left nipple. No bruises or petechiae.

4 Case 1- Initial Laboratory Studies PT 13.9 sec (11-14)PT 13.9 sec (11-14) aPTT 52.2 sec (22-32)aPTT 52.2 sec (22-32)

5 Case 1 - questions Question 1: How do we evaluate patients with an abnormal aPTT?Question 1: How do we evaluate patients with an abnormal aPTT? Question 2: What does the patient have?Question 2: What does the patient have? Question 3: How should the patient be treated?Question 3: How should the patient be treated?

6 Obligatory Confusing Coag Cascade

7 Coagulation made easy The PTT PathwayThe PT Pathway

8 Coagulation made easy X The PTT PathwayThe PT Pathway

9 Coagulation made easy VXVX The PTT PathwayThe PT Pathway

10 Coagulation made easy VXVX ProthrombinThrombin The PTT PathwayThe PT Pathway

11 Coagulation made easy VXVX ProthrombinThrombinFibrinogenFibrin The PTT PathwayThe PT Pathway

12 Coagulation made easy - the PT ProthrombinThrombinFibrinogenFibrin 7 VXVX

13 Coagulation made easy - the aPTT ProthrombinThrombinFibrinogenFibrin VXVX XII XI IX VIII

14 Coagulation made easy - the aPTT ProthrombinThrombinFibrinogenFibrin T N E T VXVX E

15 Coagulation made easy - the aPTT ProthrombinThrombinFibrinogenFibrin Twelve Nine Eight Ten VXVX Eleven

16 Deficiencies of factor XI, IX, VIII, VII. X, V, prothrombin and fibrinogen are clinically significant.Deficiencies of factor XI, IX, VIII, VII. X, V, prothrombin and fibrinogen are clinically significant. Inhibitors of these factors 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.Deficiency of Factor XII, and the presence of the lupus anticoagulant are not clinically significant. XII XI IX X VIIIVII Thrombin V Fibrinogen Fibrin What matters clinically

17 Coagulation Made Easy- The Mixing Study Useful to differentiate etiologies of prolonged clotting in a coagulation assay.Useful to differentiate etiologies of prolonged clotting in a coagulation assay. Patients plasma is mixed 50:50 with normal plasma. Coagulation assay is repeated.Patients plasma is mixed 50:50 with normal plasma. Coagulation assay is repeated. If substantial correction is noted after mix, suspect clotting factor deficiency.If substantial correction is noted after mix, suspect clotting factor deficiency. If no or minimal correction seen, suspect inhibitor.If no or minimal correction seen, suspect inhibitor.

18 Case 1 - More Laboratory Data aPTT sec (22-32)aPTT sec (22-32) aPTT mix secaPTT mix sec

19 Case 1 - More Laboratory Data aPTT sec (22-32)aPTT sec (22-32) aPTT mix secaPTT mix sec Interpretation: Factor DeficiencyInterpretation: Factor Deficiency

20 Case 1 - Which Factor(s) are deficient? ProthrombinThrombinFibrinogenFibrin Twelve Nine Eight Ten VXVX Eleven

21 Case 1 - More Laboratory Data Factor II 104% Factor V 111% Factor VIII 128% Factor IX 2% Factor X 129% Factor XI 78% Question 2: What does the patient have?

22 Hemophilia X-linked recessive disorderX-linked recessive disorder Hemophilia A - deficiency of Factor VIIIHemophilia A - deficiency of Factor VIII Hemophilia B - deficiency of Factor IXHemophilia B - deficiency of Factor IX Incidence 1/5000 live male birthsIncidence 1/5000 live male births Estimated 20,000 cases in US; 1,000 in NCEstimated 20,000 cases in US; 1,000 in NC Racial groups affected with similar frequencyRacial groups affected with similar frequency

23 Clinical Classification of Hemophilia Severe< 1% Moderate1% - 5% Mild5% - 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 Subclinical25% - 50%

24 Hemophilia Treatment Replace Deficient FactorReplace Deficient Factor Many Products: Two general categories:Many Products: Two general categories: –Plasma derived Virally inactivatedVirally inactivated Generally reserved for individuals who are HIV/HepC positiveGenerally reserved for individuals who are HIV/HepC positive –Recombinant More expensiveMore expensive Should be product of choice for all children and previously untreated patientsShould be product of choice for all children and previously untreated patients Inhibit Fibrinolysis - in mucosal bleedingInhibit Fibrinolysis - in mucosal bleeding

25 Hemophilia Treatment Clotting factor is dosed in UNITSClotting factor is dosed in UNITS One Unit = amount of factor present in 1 ml of normal plasmaOne Unit = amount of factor present in 1 ml of normal plasma Replacement Factor Dosing is based on 3 variablesReplacement 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 BleedingOptimal Factor Level Duration in days Joint or muscle GI tract Oral, nasal, GU mucosa 30-50Until healing CNS Retroperitoneal Surgery/Trauma

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.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.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.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.A 33 y.o. man presented with post-operative bleeding after a tonsillectomy. 10/15/01 – Hb/Hct = 15.3/ /15/01 – Hb/Hct = 15.3/42.7. –PT/aPTT = 13/35.6 ( ) 10/17/01 – Tonsillectomy.10/17/01 – Tonsillectomy. 10/17-10/24, pt took ibuprofen for pain10/17-10/24, pt took ibuprofen for pain 10/24 early am – Pt awoke with severe bleeding10/24 early am – Pt awoke with severe bleeding –Hb/Hct in ER 14.1/38

30 Case 2 Bleeding did not stop with ER cauterization.Bleeding did not stop with ER cauterization. Pt given platelets, FFP, then taken to ORPt given platelets, FFP, then taken to OR Notice made of persistent venous oozing and bleeding. DDAVP givenNotice made of persistent venous oozing and bleeding. DDAVP given 10/25 – Pt had persistent post-op bleeding10/25 – Pt had persistent post-op bleeding H/H eventually reached 9.1/25H/H eventually reached 9.1/25

31 Case 2 Bleeding History: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 30s.FHx - sister with easy bruising and abnormal menstrual bleeding. Mother had hysterectomy in early 30s.

32 Case 2 - Questions Question #1 - What is a reasonable screening evaluation for patients pre-operatively?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 #2 - What is a reasonable screening evaluation for patients with a positive bleeding history? Question #3 - What does the patient have?Question #3 - What does the patient have? Question #4 - How should the patient be treated prior to future surgical interventions?Question #4 - How should the patient be treated prior to future surgical interventions?

33 Case 2 PT seconds. (11-14)PT seconds. (11-14) aPTT seconds ( ).aPTT seconds ( ). Platelet function screen.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 Prolonged in cases of platelet dysfunction (acquired or congenital) or von Willebrands 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 Pre-DDAVPPost-DDAVP Col/epi >300 sec 133 sec Col/ADP 98 sec 56 sec vWF antigen 67%151% vWF activity 78%219% Question #3: How should the patient be treated prior to future invasive procedures?

39 Case 2 The patient was told he had mild Type I von Willebrands 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.Take a bleeding history. Then, write it down. Not all bleeding diatheses show up with a PT/PTT.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).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.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 Intrinsic pathway XI, IX, VIII Extrinsic pathway TF, VII Xa generation Thrombin Generation

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 DiseaseDIC 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 1.IF PLATELETS FALL ON HEPARIN, STOP HEPARIN IMMEDIATELY. 2.Stop heparin 3.Stop heparin 4.Use a different anticoagulant 1.Lepirudin 2.Argatroban 3.Bivalirudin (off label) 4.Fondaparinux (off-label)

62 HIT Testing TestAdvantagesDisadvantages HIPA Specificity: high Sensitivity: low Rapid turn around timeTechnique-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 thrombinRecombinant protein, irreversibly binds to and inactivates thrombin Associated with increased bleeding, compared to heparin.Associated with increased bleeding, compared to heparin. Short t 1/2.Short t 1/2. Renally excreted.Renally excreted. Antibody formation is commonAntibody formation is common –decrease clearance and potentiate anticoagulation effect. –Allergic reactions may occur Monitor by using aPTT (aim for sec)Monitor by using aPTT (aim for sec)

64 Argatroban Synthetic direct thrombin inhibitorSynthetic direct thrombin inhibitor Reversibly binds to thrombins catalytic siteReversibly binds to thrombins catalytic site Associated with increased bleeding compared to heparinAssociated with increased bleeding compared to heparin Short t 1/2 - must give as continuous infusion - no loading doseShort 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)Dose is 0.2 mcg/kg/min (maximum dose is 10 mcg/kg/min) Monitor using the aPTT (aim for aPTT 50-80)Monitor using the aPTT (aim for aPTT 50-80) Hepatically cleared - reduce dose by 75% in liver failure.Hepatically cleared - reduce dose by 75% in liver failure. Prolongs the PT.Prolongs the PT.

65 Fondaparinux Derived from AT-binding moiety of heparin.Derived from AT-binding moiety of heparin. Leads to indirect inhibition of Xa.Leads to indirect inhibition of Xa. Once daily SQ therapyOnce daily SQ therapy Renally clearedRenally cleared Approved for treatment of VTE and prophylaxis of patients at high risk for VTE (hip, knee surgery, abdominal surgery)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 A.Proceed with the transfusion. B.Have another health care professional witness the patients confirmation of her ID, then proceed with the transfusion. C.Check the patients wrist ID band against the red cell bag tag, along with another health care professional witness, then proceed with the transfusion. D.Check the patients 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 patients 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 A.Draw blood cultures, administer acetominophen, then proceed with the transfusion before the unit of platelets expire. B.Draw blood cultures, administer acetominophen, then proceed with the transfusion when the temperature reaches baseline. C.Draw blood cultures, change antibiotics, administer acetominophen, then proceed with the transfusion when the temperature reaches baseline. D.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 A.Order 2 doses of platelets for transfusion. B.Order 2 doses of platelets for transfusion, then check platelet count in the morning before procedure. C.Order 1 dose of platelets for transfusion, then check platelet count in the morning before procedure. D.Order 1 dose of platelets for transfusion, then check platelet count before ordering another dose of platelets.


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