Hematologic/CoagulationHematologic/Coagulation
Cases in Critical CareCases in Critical Care
Alice Ma, M.D.Alice Ma, M.D.
U...
Case 1Case 1
• A 21 y.o. UNC student presented to the coagulationA 21 y.o. UNC student presented to the coagulation
clinic...
Case 1Case 1
• Family History - mother is on iron forFamily History - mother is on iron for
unknown reasons. Maternal gran...
Case 1- Initial Laboratory StudiesCase 1- Initial Laboratory Studies
• PT 13.9 sec (11-14)PT 13.9 sec (11-14)
• aPTT 52.2 ...
Case 1 - questionsCase 1 - questions
• Question 1: How do we evaluateQuestion 1: How do we evaluate
patients with an abnor...
Obligatory Confusing Coag CascadeObligatory Confusing Coag Cascade
Coagulation made easyCoagulation made easy
The PTT Pathway The PT Pathway
Coagulation made easyCoagulation made easy
X
The PTT Pathway The PT Pathway
Coagulation made easyCoagulation made easy
V
X
The PTT Pathway The PT Pathway
Coagulation made easyCoagulation made easy
V
X
Prothrombin Thrombin
The PTT Pathway The PT Pathway
Coagulation made easyCoagulation made easy
V
X
Prothrombin Thrombin
Fibrinogen Fibrin
The PTT Pathway The PT Pathway
Coagulation made easy - the PTCoagulation made easy - the PT
Prothrombin Thrombin
Fibrinogen Fibrin
7
V
X
Coagulation made easy - the aPTTCoagulation made easy - the aPTT
Prothrombin Thrombin
Fibrinogen Fibrin
V
X
XII
XI
IX
VIII
Coagulation made easy - the aPTTCoagulation made easy - the aPTT
Prothrombin Thrombin
Fibrinogen Fibrin
T
N
E
T
V
X
E
Coagulation made easy - the aPTTCoagulation made easy - the aPTT
Prothrombin Thrombin
Fibrinogen Fibrin
Twelve
Nine
Eight
...
• Deficiencies of factor XI,Deficiencies of factor XI,
IX, VIII, VII. X, V,IX, VIII, VII. X, V,
prothrombin andprothrombin...
Coagulation Made Easy- The Mixing StudyCoagulation Made Easy- The Mixing Study
• Useful to differentiate etiologies of pro...
Case 1 - More Laboratory DataCase 1 - More Laboratory Data
• aPTT - 52.2 sec (22-32)aPTT - 52.2 sec (22-32)
• aPTT mix - 3...
Case 1 - More Laboratory DataCase 1 - More Laboratory Data
• aPTT - 52.2 sec (22-32)aPTT - 52.2 sec (22-32)
• aPTT mix - 3...
Case 1 - Which Factor(s) are deficient?Case 1 - Which Factor(s) are deficient?
Prothrombin Thrombin
Fibrinogen Fibrin
Twel...
Case 1 - More Laboratory DataCase 1 - More Laboratory Data
Factor IIFactor II 104%104%
Factor VFactor V 111%111%
Factor VI...
HemophiliaHemophilia
• X-linked recessive disorderX-linked recessive disorder
• Hemophilia A - deficiency of Factor VIIIHe...
Clinical Classification of HemophiliaClinical Classification of Hemophilia
Severe < 1%
Moderate 1% - 5%
Mild 5% - 25%
Seve...
Hemophilia TreatmentHemophilia Treatment
• Replace Deficient FactorReplace Deficient Factor
• Many Products: Two general c...
Hemophilia TreatmentHemophilia Treatment
• Clotting factor is dosed in UNITSClotting factor is dosed in UNITS
• One Unit =...
Hemophilia Treatment
Site of Bleeding Optimal Factor
Level
Duration in days
Joint or muscle 30-50 1-2
GI tract 40-60 7-10
...
Case 1 - Followup
• The patient was given a bolus dose of 4,000 units
of BeneFIX (recombinant Factor IX) calculated to
rai...
Teaching PointsTeaching Points
• A prolonged PTT should be evaluated first byA prolonged PTT should be evaluated first by
...
Case 2Case 2
• A 33 y.o. man presented with post-operativeA 33 y.o. man presented with post-operative
bleeding after a ton...
Case 2Case 2
• Bleeding did not stop with ER cauterization.Bleeding did not stop with ER cauterization.
• Pt given platele...
Case 2Case 2
• Bleeding History:Bleeding History:
– Lifelong nosebleedsLifelong nosebleeds
– Gum bleeding with brushing te...
Case 2 - QuestionsCase 2 - Questions
• Question #1 - What is a reasonable screeningQuestion #1 - What is a reasonable scre...
Case 2
• PT - 12.9 seconds. (11-14)PT - 12.9 seconds. (11-14)
• aPTT - 33.9 seconds (22-33.4).aPTT - 33.9 seconds (22-33.4...
The platelet function screen
• An in vitro method to test primary hemostasis
• Measures the length of time for whole citra...
The platelet function screen
The platelet function screen
• Prolonged in cases of platelet dysfunction
(acquired or congenital) or von Willebrand’s
dis...
Case 2 - More laboratory data
• vWF antigen - 58%
• vWF activity - 50%
• Platelet aggregation studies: abnormal
aggregatio...
Case 2Case 2
Pre-DDAVPPre-DDAVP Post-DDAVPPost-DDAVP
Col/epiCol/epi >300 sec>300 sec 133 sec133 sec
Col/ADPCol/ADP 98 sec9...
Case 2
• The patient was told he had mild Type I von
Willebrand’s disease, coupled with a mild platelet
dysfunction. He su...
Teaching PointsTeaching Points
• Take a bleeding history. Then, write it down.Take a bleeding history. Then, write it down...
Bleeding History
• Nosebleeds
• Gum bleeding
• Bleeding with (wisdom) tooth extraction
• Easy bruisability
• Bleeding with...
Case 3
• A 72 y.o. man suffered complications of an MVA
with multiple fractures and splenic rupture 7 days
prior. He is no...
Case 3 - Questions
• Q1. What blood products should be given to the
patient?
• Q2. What are the indications for use of Nov...
What blood products to give?
• H/H 7/21, Plts 14, PT 33, PTT 60 Fibrinogen 81
• Platelets - With active hemorrhage, try to...
Review Cascade model of hemostasis
Intrinsic pathwayIntrinsic pathway
XI, IX, VIIIXI, IX, VIII
Extrinsic pathwayExtrinsic ...
A Cell-Based Model of Hemostasis
• Initiation
• Amplification
• Propagation
Initiation
Amplification
Propagation
Hemostasis
Hemophilia is a Defect in Plateetl
Surface Thrombin Generation
NovoSeven can Ameliorate the
Defect in Hemophilia
NovoSeven Augments Thrombin Generation on the
Platelet Surface in Non-Hemophilics
NovoSeven in Surgery/Trauma
• This is an Off-Label Use
• Pts are at significant risk for thrombosis,
especially if they ha...
Case 4
• A patient presents with a perforated diverticular
abscess. He has alcoholic cirrhosis and poor
nutrition.
• His P...
Case 4
Vitamin K
Deficiency
Liver Disease DIC
Factor V ← ↓ ↓↓
Factor VII ↓↓ ↓↓ ↓↓
Factor VIII ← ↑↑ ← /↓
Case 5
• A 65 y.o. female smoker with a h/o peripheral
vascular disease presented to the ER with
unstable angina. She was ...
Case 5
• On hospital day #12, the patient developed acute
left leg swelling and a DVT was diagnosed by
ultrasound. Platele...
HIT
• Seen in 1-3% of patients treated with heparin
• Usually, 7-10 d after heparin started, platelets fall by at
least 1/...
Alternate Presentations of HIT/T
• Small drop in platelet count (especially with
skin necrosis)
• Earlier onset thrombocyt...
HIT/T treatment
1. IF PLATELETS FALL ON HEPARIN, STOP
HEPARIN IMMEDIATELY.
2. Stop heparin
3. Stop heparin
4. Use a differ...
HIT Testing
Test Advantages Disadvantages
HIPAHIPA Specificity: highSpecificity: high Sensitivity: lowSensitivity: low
Rap...
LepirudinLepirudin
• Recombinant protein, irreversibly binds to andRecombinant protein, irreversibly binds to and
inactiva...
ArgatrobanArgatroban
• Synthetic direct thrombin inhibitorSynthetic direct thrombin inhibitor
• Reversibly binds to thromb...
FondaparinuxFondaparinux
• Derived from AT-binding moiety of heparin.Derived from AT-binding moiety of heparin.
• Leads to...
Case 6
• A 72 y.o. woman requires red cell transfusion for
symptomatic anemia. Red cells are delivered to
the bedside. The...
Case 6
A. Proceed with the transfusion.
B. Have another health care professional witness the
patient’s confirmation of her...
Case 7
• A patient in the SICU is in the process of
receiving a transfusion of platelets for a platelet
count of 8. Midway...
Case 7
A. Draw blood cultures, administer acetominophen, then proceed
with the transfusion before the unit of platelets ex...
Case 8
• A patient with aplastic anemia is scheduled to
undergo breast biopsy in the morning. Her
platelet count is 4. Wha...
Case 8
A. Order 2 doses of platelets for transfusion.
B. Order 2 doses of platelets for transfusion, then check
platelet c...
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  1. 1. Hematologic/CoagulationHematologic/Coagulation Cases in Critical CareCases in Critical Care Alice Ma, M.D.Alice Ma, M.D. University of North Carolina-Chapel HillUniversity of North Carolina-Chapel Hill Division of HematologyDivision of Hematology
  2. 2. Case 1Case 1 • A 21 y.o. UNC student presented to the coagulationA 21 y.o. UNC student presented to the coagulation clinic from the plastic surgery clinic. He hadclinic from the plastic surgery clinic. He had undergone nipple piercing 11 days prior and hadundergone nipple piercing 11 days prior and had prolonged bleeding, requiring 2 trips to theprolonged bleeding, requiring 2 trips to the emergency room, gelfoam application, pressureemergency room, gelfoam application, pressure dressing, stitching, re-stitching. He was still activelydressing, stitching, re-stitching. He was still actively bleeding.bleeding. • PMHx was notable for tongue laceration at age 7PMHx was notable for tongue laceration at age 7 following a fall, with persistent bleeding. Thumbfollowing a fall, with persistent bleeding. Thumb injury with persistent bleeding, ganglion cyst removalinjury with persistent bleeding, ganglion cyst removal without abnormal bleeding.without abnormal bleeding.
  3. 3. Case 1Case 1 • Family History - mother is on iron forFamily History - mother is on iron for unknown reasons. Maternal grandmotherunknown reasons. Maternal grandmother may have abnormal bleeding (pt unsure)may have abnormal bleeding (pt unsure) Sister alive and well without abnormalSister alive and well without abnormal bleeding.bleeding. • Meds - noneMeds - none • SHx - senior at UNC, occasional alcohol, noSHx - senior at UNC, occasional alcohol, no tobacco or drugstobacco or drugs • PEx - actively bleeding left nipple. No bruisesPEx - actively bleeding left nipple. No bruises or petechiae.or petechiae.
  4. 4. Case 1- Initial Laboratory StudiesCase 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. 5. Case 1 - questionsCase 1 - questions • Question 1: How do we evaluateQuestion 1: How do we evaluate patients with an abnormal aPTT?patients with an abnormal aPTT? • Question 2: What does the patientQuestion 2: What does the patient have?have? • Question 3: How should the patientQuestion 3: How should the patient be treated?be treated?
  6. 6. Obligatory Confusing Coag CascadeObligatory Confusing Coag Cascade
  7. 7. Coagulation made easyCoagulation made easy The PTT Pathway The PT Pathway
  8. 8. Coagulation made easyCoagulation made easy X The PTT Pathway The PT Pathway
  9. 9. Coagulation made easyCoagulation made easy V X The PTT Pathway The PT Pathway
  10. 10. Coagulation made easyCoagulation made easy V X Prothrombin Thrombin The PTT Pathway The PT Pathway
  11. 11. Coagulation made easyCoagulation made easy V X Prothrombin Thrombin Fibrinogen Fibrin The PTT Pathway The PT Pathway
  12. 12. Coagulation made easy - the PTCoagulation made easy - the PT Prothrombin Thrombin Fibrinogen Fibrin 7 V X
  13. 13. Coagulation made easy - the aPTTCoagulation made easy - the aPTT Prothrombin Thrombin Fibrinogen Fibrin V X XII XI IX VIII
  14. 14. Coagulation made easy - the aPTTCoagulation made easy - the aPTT Prothrombin Thrombin Fibrinogen Fibrin T N E T V X E
  15. 15. Coagulation made easy - the aPTTCoagulation made easy - the aPTT Prothrombin Thrombin Fibrinogen Fibrin Twelve Nine Eight Ten V X Eleven
  16. 16. • Deficiencies of factor XI,Deficiencies of factor XI, IX, VIII, VII. X, V,IX, VIII, VII. X, V, prothrombin andprothrombin and fibrinogen are clinicallyfibrinogen are clinically significant.significant. • Inhibitors of these factorsInhibitors of these factors are clinically significant.are clinically significant. • Deficiency of Factor XII,Deficiency of Factor XII, and the presence of theand the presence of the lupus anticoagulant arelupus anticoagulant are not clinically significant.not clinically significant. XII XI IX X VIII VII Thrombin V Fibrinogen Fibrin What matters clinically
  17. 17. Coagulation Made Easy- The Mixing StudyCoagulation Made Easy- The Mixing Study • Useful to differentiate etiologies of prolongedUseful to differentiate etiologies of prolonged clotting in a coagulation assay.clotting in a coagulation assay. • Patient’s plasma is mixed 50:50 with normalPatient’s plasma is mixed 50:50 with normal plasma. Coagulation assay is repeated.plasma. Coagulation assay is repeated. • If “substantial” correction is noted after mix,If “substantial” correction is noted after mix, suspectsuspect clotting factor deficiencyclotting factor deficiency.. • If no or minimal correction seen, suspectIf no or minimal correction seen, suspect inhibitorinhibitor..
  18. 18. Case 1 - More Laboratory DataCase 1 - More Laboratory Data • aPTT - 52.2 sec (22-32)aPTT - 52.2 sec (22-32) • aPTT mix - 31.5 secaPTT mix - 31.5 sec
  19. 19. Case 1 - More Laboratory DataCase 1 - More Laboratory Data • aPTT - 52.2 sec (22-32)aPTT - 52.2 sec (22-32) • aPTT mix - 31.5 secaPTT mix - 31.5 sec • Interpretation:Interpretation: Factor DeficiencyFactor Deficiency
  20. 20. Case 1 - Which Factor(s) are deficient?Case 1 - Which Factor(s) are deficient? Prothrombin Thrombin Fibrinogen Fibrin Twelve Nine Eight Ten V X Eleven
  21. 21. Case 1 - More Laboratory DataCase 1 - More Laboratory Data Factor IIFactor II 104%104% Factor VFactor V 111%111% Factor VIIIFactor VIII 128%128% Factor IXFactor IX 2%2% Factor XFactor X 129%129% Factor XIFactor XI 78%78% Question 2: What does the patient have?Question 2: What does the patient have?
  22. 22. HemophiliaHemophilia • X-linked recessive disorderX-linked recessive disorder • Hemophilia A - deficiency of Factor VIIIHemophilia A - deficiency of Factor VIII • Hemophilia BHemophilia B - deficiency of Factor IX- 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. 23. Clinical Classification of HemophiliaClinical Classification of Hemophilia Severe < 1% Moderate 1% - 5% Mild 5% - 25% Severe hemarthrosisSevere hemarthrosis Spontaneous bleedingSpontaneous bleeding Serious bleeding afterSerious bleeding after minor traumaminor trauma Bleeding after surgeryBleeding after surgery or traumaor trauma Moderate bleeding afterModerate bleeding after trauma or surgerytrauma or surgery TypeType FVIII/IX activityFVIII/IX activity Clinical pictureClinical picture Subclinical 25% - 50%
  24. 24. Hemophilia TreatmentHemophilia Treatment • Replace Deficient FactorReplace Deficient Factor • Many Products: Two general categories:Many Products: Two general categories: – Plasma derivedPlasma derived • Virally inactivatedVirally inactivated • Generally reserved for individuals who are HIV/HepCGenerally reserved for individuals who are HIV/HepC positivepositive – RecombinantRecombinant • More expensiveMore expensive • Should be product of choice for all children andShould be product of choice for all children and previously untreated patientspreviously untreated patients • Inhibit Fibrinolysis - in mucosal bleedingInhibit Fibrinolysis - in mucosal bleeding
  25. 25. Hemophilia TreatmentHemophilia Treatment • Clotting factor is dosed in UNITSClotting factor is dosed in UNITS • One Unit = amount of factor present in 1 ml ofOne Unit = amount of factor present in 1 ml of normal plasmanormal plasma • Replacement Factor Dosing is based on 3Replacement Factor Dosing is based on 3 variablesvariables – Volume of distributionVolume of distribution (extravascula/intravascular)(extravascula/intravascular) – Half-lifeHalf-life – Level of factor required for hemostasisLevel of factor required for hemostasis
  26. 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. 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. 28. Teaching PointsTeaching Points • A prolonged PTT should be evaluated first byA prolonged PTT should be evaluated first by mixing study, then with factor levels, ifmixing study, then with factor levels, if appropriate.appropriate. • Hemophilia can be undiagnosed untilHemophilia can be undiagnosed until adulthood, especially if mild or moderate.adulthood, especially if mild or moderate. • Treating hemophilia is expensive andTreating hemophilia is expensive and complicated, and patients should be followedcomplicated, and patients should be followed in a comprehensive hemophilia center.in a comprehensive hemophilia center.
  29. 29. Case 2Case 2 • A 33 y.o. man presented with post-operativeA 33 y.o. man presented with post-operative bleeding after a tonsillectomy.bleeding after a tonsillectomy. • 10/15/01 – Hb/Hct = 15.3/42.7.10/15/01 – Hb/Hct = 15.3/42.7. – PT/aPTT = 13/35.6 (22-33.4)PT/aPTT = 13/35.6 (22-33.4) • 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 14.1/38Hb/Hct in ER 14.1/38
  30. 30. Case 2Case 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 andNotice made of persistent venous oozing and bleeding. DDAVP givenbleeding. 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. 31. Case 2Case 2 • Bleeding History:Bleeding History: – Lifelong nosebleedsLifelong nosebleeds – Gum bleeding with brushing teethGum bleeding with brushing teeth – Prolonged bleeding with nicksProlonged bleeding with nicks – Bleeding with multiple tooth extractions (characterized asBleeding with multiple tooth extractions (characterized as delayed)delayed) – appy at age 19, wound dehisced and bledappy at age 19, wound dehisced and bled • FHx - sister with easy bruising and abnormalFHx - sister with easy bruising and abnormal menstrual bleeding. Mother had hysterectomy inmenstrual bleeding. Mother had hysterectomy in early 30’s.early 30’s.
  32. 32. Case 2 - QuestionsCase 2 - Questions • Question #1 - What is a reasonable screeningQuestion #1 - What is a reasonable screening evaluation for patients pre-operatively?evaluation for patients pre-operatively? • Question #2 - What is a reasonable screeningQuestion #2 - What is a reasonable screening evaluation for patients with a positive bleedingevaluation for patients with a positive bleeding history?history? • Question #3 - What does the patient have?Question #3 - What does the patient have? • Question #4 - How should the patient beQuestion #4 - How should the patient be treated prior to future surgical interventions?treated prior to future surgical interventions?
  33. 33. Case 2 • PT - 12.9 seconds. (11-14)PT - 12.9 seconds. (11-14) • aPTT - 33.9 seconds (22-33.4).aPTT - 33.9 seconds (22-33.4). • Platelet function screen.Platelet function screen. – col/epi closure timecol/epi closure time >300 sec>300 sec (84-178)(84-178) – col/ADP closure timecol/ADP closure time 136 sec136 sec (60-107)(60-107)
  34. 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. 35. The platelet function screen
  36. 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. 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. 38. Case 2Case 2 Pre-DDAVPPre-DDAVP Post-DDAVPPost-DDAVP Col/epiCol/epi >300 sec>300 sec 133 sec133 sec Col/ADPCol/ADP 98 sec98 sec 56 sec56 sec vWF antigenvWF antigen 67%67% 151%151% vWF activityvWF activity 78%78% 219%219% Question #3: How should the patient be treated prior toQuestion #3: How should the patient be treated prior to future invasive procedures?future invasive procedures?
  39. 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. 40. Teaching PointsTeaching Points • Take a bleeding history. Then, write it down.Take a bleeding history. Then, write it down. • Not all bleeding diatheses show up with aNot all bleeding diatheses show up with a PT/PTT.PT/PTT. • Defects in primary hemostasis causeDefects in primary hemostasis cause mucocutaneous bleeding (“Oozing andmucocutaneous bleeding (“Oozing and Bruising”) and are best screened for by usingBruising”) and are best screened for by using the platelet function screen (PFA-100).the platelet function screen (PFA-100). • DDAVP can improve primary hemostasis.DDAVP can improve primary hemostasis.
  41. 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. 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. 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. 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. 45. Review Cascade model of hemostasis Intrinsic pathwayIntrinsic pathway XI, IX, VIIIXI, IX, VIII Extrinsic pathwayExtrinsic pathway TF, VIITF, VII Xa generationXa generation Thrombin GenerationThrombin Generation
  46. 46. A Cell-Based Model of Hemostasis • Initiation • Amplification • Propagation
  47. 47. Initiation
  48. 48. Amplification
  49. 49. Propagation
  50. 50. Hemostasis
  51. 51. Hemophilia is a Defect in Plateetl Surface Thrombin Generation
  52. 52. NovoSeven can Ameliorate the Defect in Hemophilia
  53. 53. NovoSeven Augments Thrombin Generation on the Platelet Surface in Non-Hemophilics
  54. 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. 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. 56. Case 4 Vitamin K Deficiency Liver Disease DIC Factor V ← ↓ ↓↓ Factor VII ↓↓ ↓↓ ↓↓ Factor VIII ← ↑↑ ← /↓
  57. 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. 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. 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. 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. 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. 62. HIT Testing Test Advantages Disadvantages HIPAHIPA Specificity: highSpecificity: high Sensitivity: lowSensitivity: low Rapid turn around timeRapid turn around time Technique-dependentTechnique-dependent ELISAELISA Sensitivity: highSensitivity: high Specificity: low (false-positivesSpecificity: low (false-positives Technically easyTechnically easy high for some populations)high for some populations) Poor concordance with SRAPoor 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. 63. LepirudinLepirudin • Recombinant protein, irreversibly binds to andRecombinant protein, irreversibly binds to and inactivates thrombininactivates thrombin • Associated with increased bleeding, compared toAssociated with increased bleeding, compared to heparin.heparin. • Short tShort t 1/21/2.. • Renally excreted.Renally excreted. • Antibody formation is commonAntibody formation is common – decrease clearance and potentiate anticoagulationdecrease clearance and potentiate anticoagulation effect.effect. – Allergic reactions may occurAllergic reactions may occur • Monitor by using aPTT (aim for 50-70 sec)Monitor by using aPTT (aim for 50-70 sec)
  64. 64. ArgatrobanArgatroban • Synthetic direct thrombin inhibitorSynthetic direct thrombin inhibitor • Reversibly binds to thrombin’s catalytic siteReversibly binds to thrombin’s catalytic site • Associated with increased bleeding compared to heparinAssociated with increased bleeding compared to heparin • Short tShort t 1/21/2 - must give as continuous infusion - no loading- must give as continuous infusion - no loading dosedose • 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. 65. FondaparinuxFondaparinux • 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 ofApproved for treatment of VTE and prophylaxis of patients at high risk for VTE (hip, knee surgery,patients at high risk for VTE (hip, knee surgery, abdominal surgery)abdominal surgery) • Not approved for use in HIT
  66. 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. 67. Case 6 A. Proceed with the transfusion. B. Have another health care professional witness the patient’s confirmation of her ID, then proceed with the transfusion. C. 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. D. 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. 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. 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. 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. 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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