Presentation on theme: "Hematologic/Coagulation Cases in Critical Care"— Presentation transcript:
1Hematologic/Coagulation Cases in Critical Care Alice Ma, M.D.University of North Carolina-Chapel HillDivision of Hematology
2Case 1A 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.
3Case 1Family History - mother is on iron for unknown reasons. Maternal grandmother may have abnormal bleeding (pt unsure) Sister alive and well without abnormal bleeding.Meds - noneSHx - senior at UNC, occasional alcohol, no tobacco or drugsPEx - actively bleeding left nipple. No bruises or petechiae.
7Coagulation made easyThe PTT PathwayThe PT Pathway
8Coagulation made easyThe PTT PathwayThe PT PathwayX
9Coagulation made easyThe PTT PathwayThe PT PathwayVX
10X Coagulation made easy Prothrombin Thrombin The PTT Pathway The PT PathwayVXProthrombinThrombin
11X Coagulation made easy Prothrombin Thrombin Fibrinogen Fibrin The PTT PathwayThe PT PathwayVXProthrombinThrombinFibrinogenFibrin
12Coagulation made easy - the PT 7VXProthrombinThrombinFibrinogenFibrin
13Coagulation made easy - the aPTT XIIXIIXVXVIIIProthrombinThrombinFibrinogenFibrin
14Coagulation made easy - the aPTT VXTProthrombinThrombinFibrinogenFibrin
15Coagulation made easy - the aPTT TwelveElevenNineEightVXTenProthrombinThrombinFibrinogenFibrin
16What matters clinically XIIXIDeficiencies 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.IXVIIIVIIXVThrombinFibrinogen Fibrin
17Coagulation 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.
18Case 1 - More Laboratory Data aPTT sec (22-32)aPTT mix sec
19Case 1 - More Laboratory Data aPTT sec (22-32)aPTT mix secInterpretation: Factor Deficiency
20Case 1 - Which Factor(s) are deficient? TwelveElevenNineEightVXTenProthrombinThrombinFibrinogenFibrin
21Case 1 - More Laboratory Data Question 2: What does the patient have?Factor II104%Factor V111%Factor VIII128%Factor IX2%Factor X129%Factor XI78%
22Hemophilia X-linked recessive disorder Hemophilia A - deficiency of Factor VIIIHemophilia B - deficiency of Factor IXIncidence 1/5000 live male birthsEstimated 20,000 cases in US; 1,000 in NCRacial groups affected with similar frequency
23Clinical Classification of Hemophilia TypeFVIII/IX activityClinical pictureSevere < 1%Moderate 1% - 5%Mild 5% - 25%Severe hemarthrosisSpontaneous bleedingSerious bleeding afterminor traumaBleeding after surgeryor traumaModerate bleeding aftertrauma or surgerySubclinical 25% - 50%
24Hemophilia Treatment Replace Deficient Factor Many Products: Two general categories:Plasma derivedVirally inactivatedGenerally reserved for individuals who are HIV/HepC positiveRecombinantMore expensiveShould be product of choice for all children and previously untreated patientsInhibit Fibrinolysis - in mucosal bleeding
25Hemophilia Treatment Clotting factor is dosed in UNITS One Unit = amount of factor present in 1 ml of normal plasmaReplacement Factor Dosing is based on 3 variablesVolume of distribution (extravascula/intravascular)Half-lifeLevel of factor required for hemostasis
26Hemophilia Treatment Site of Bleeding Optimal Factor Level Duration in daysJoint or muscle30-501-2GI tract40-607-10Oral, nasal, GU mucosaUntil healingCNS80-10010-21Retroperitoneal7-14Surgery/Trauma7-21
27Case 1 - FollowupThe 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.
28Teaching PointsA 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.
29Case 2A 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 ( )10/17/01 – Tonsillectomy.10/17-10/24, pt took ibuprofen for pain10/24 early am – Pt awoke with severe bleedingHb/Hct in ER 14.1/38
30Case 2 Bleeding did not stop with ER cauterization. Pt given platelets, FFP, then taken to ORNotice made of persistent venous oozing and bleeding. DDAVP given10/25 – Pt had persistent post-op bleedingH/H eventually reached 9.1/25
31Case 2 Bleeding History: Lifelong nosebleedsGum bleeding with brushing teethProlonged bleeding with nicksBleeding with multiple tooth extractions (characterized as delayed)appy at age 19, wound dehisced and bledFHx - sister with easy bruising and abnormal menstrual bleeding. Mother had hysterectomy in early 30’s.
32Case 2 - QuestionsQuestion #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?
33Case 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)
34The platelet function screen An in vitro method to test primary hemostasisMeasures 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
36The 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!!
37Case 2 - More laboratory data vWF antigen - 58%vWF activity - 50%Platelet aggregation studies: abnormal aggregation in response to epinephrine, ADP, arachidonic acid.
38Case 2 Pre-DDAVP Post-DDAVP Col/epi >300 sec 133 sec Col/ADP 98 sec Question #3: How should the patient be treated prior to future invasive procedures?Pre-DDAVPPost-DDAVPCol/epi>300 sec133 secCol/ADP98 sec56 secvWF antigen67%151%vWF activity78%219%
39Case 2The 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.
40Teaching 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.
41Bleeding History Nosebleeds Gum bleeding Bleeding with (wisdom) tooth extractionEasy bruisabilityBleeding with surgeries (including circumcision)Include timing of bleedingMenstrual bleedingTransfusion requirementsFamily history of bleedingHysterectomies at an early ageBleeding with surgeries
42Case 3A 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 81After transfusion of 4 units PRBC, H/H only 8/23
43Case 3 - QuestionsQ1. What blood products should be given to the patient?Q2. What are the indications for use of Novo-Seven in the bleeding surgical patient?
44What blood products to give? H/H 7/21, Plts 14, PT 33, PTT 60 Fibrinogen 81Platelets - With active hemorrhage, try to keep platelets > 50. If no bleeding, keep platelets >10Cryoprecipitate - With active bleeding, keep fibrinogen >100. Cryo also contains FVIII, VWF, FXIIIRBCs - With active bleeding and thrombocytopenia, plts will work better if Hgb >10
45Review Cascade model of hemostasis Intrinsic pathwayXI, IX, VIIIExtrinsic pathwayTF, VIIXa generationThrombin Generation
46A Cell-Based Model of Hemostasis InitiationAmplificationPropagation
51Hemophilia is a Defect in Plateetl Surface Thrombin Generation
52NovoSeven can Ameliorate the Defect in Hemophilia
53NovoSeven Augments Thrombin Generation on the Platelet Surface in Non-Hemophilics
54NovoSeven in Surgery/Trauma This is an Off-Label UsePts 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, soFix the Plts, PT, PTT, Fibrinogen.If pt still bleeding, can then give rVIIa
55Case 4A 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 800How can we use factor levels to determine the cause of his coagulopathy?
56Case 4 Vitamin K Deficiency Liver Disease DIC Factor V Factor VIIFactor VIII /
57Case 5A 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 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 Post-op platelet count was 90.
58Case 5On hospital day #12, the patient developed acute left leg swelling and a DVT was diagnosed by ultrasound. Platelet count was 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
59HIT 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
60Alternate Presentations of HIT/T Small drop in platelet count (especially with skin necrosis)Earlier onset thrombocytopenia with heparin re-exposureDelayed-onset thrombocytopenia/ thrombosis after stopping heparinThrombosis after heparin exposure
61HIT/T treatmentIF PLATELETS FALL ON HEPARIN, STOP HEPARIN IMMEDIATELY.Stop heparinUse a different anticoagulantLepirudinArgatrobanBivalirudin (off label)Fondaparinux (off-label)
62HIT Testing Test Advantages Disadvantages HIPA Specificity: high Sensitivity: low Rapid turn around time Technique-dependentELISA Sensitivity: high Specificity: low (false-positives Technically easy high for some populations) Poor concordance with SRAThere is no Gold Standard in diagnostic testing;HIT is a clinical diagnosisPts Must Be off heparin for 16 hours prior to testing
63LepirudinRecombinant protein, irreversibly binds to and inactivates thrombinAssociated with increased bleeding, compared to heparin.Short t 1/2.Renally excreted.Antibody formation is commondecrease clearance and potentiate anticoagulation effect.Allergic reactions may occurMonitor by using aPTT (aim for sec)
64Argatroban Synthetic direct thrombin inhibitor Reversibly binds to thrombin’s catalytic siteAssociated with increased bleeding compared to heparinShort t 1/2 - must give as continuous infusion - no loading doseDose 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.
65Fondaparinux Derived from AT-binding moiety of heparin. Leads to indirect inhibition of Xa.Once daily SQ therapyRenally clearedApproved for treatment of VTE and prophylaxis of patients at high risk for VTE (hip, knee surgery, abdominal surgery)Not approved for use in HIT
66Case 6A 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?
67Case 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.
68Case 7A 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 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?
69Case 7Draw 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.
70Case 8A 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?
71Case 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.