COAGULATION EMERGENCIES

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COAGULATION EMERGENCIES

• How to deal with/avoid a bloodbath

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COAGULATION EMERGENCIES

• Congenital Coagulation Abnormalities
• Hemophilia
• Von Willebrand disease
• ITP
• Dilutional Coagulopathy
• Massive Medical/Surgical Bleeding
• TTP/HUS
• Acquired Bleeding/Clotting Disorders
• Inhibitors

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Case 1

• 27 year old man, known mild hemophilia B,
  presents to ER with massive GI bleed. 2 days
  previously had been placed on Naproxen for a
  twisted knee.

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HEMOPHILIA

• Sex-linked recessive bleeding disorder
• Disease dates at least back to days of Talmud
• Incidence 20/100,000 males
• 85 Hemophilia A, 15 Hemophilia B
• Clinically indistinguishable except by factor
  analysis
• Genetic lethal prior to replacement therapy

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HEMOPHILIA

• Mild - gt 5 activity bleeding only with trauma
  or surgery
• Moderate 1-5 activity - Bleeding with minor
  trauma occasional spontaneous hemarthroses
• Severe - lt 1 activity Spontaneous hemarthroses
  soft tissue bleeds

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HEMOPHILIA General Rules RE Rx

• Treat first ask questions later
• Bleeding into closed spaces stops!!
• AVOID EMERGENT PROCEDURES IF POSSIBLE
• No procedures without replacement Rx
• Avoid weekend/night procedures
• No procedures without Hematology Lab backup

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INITIAL Rx OF HEMOPHILIA A
Indication Factor VIII Desired Level () Factor VIII administered (units/kg)
Mild hemorrhage 30 15
Moderate hemorrhage 50 25
Major hemorrhage 80-100 40-50
Usual Product Monoclonal Purified F VIII
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INITIAL Rx OF HEMOPHILIA B
Indication Factor IX Desired Level () Factor IX Administered (units/kg)
Mild hemorrhage 30 30
Moderate hemorrhage 50 50
Major hemorrhage 80-100 80-100
Usual Product Recombinant or Monoclonal F IX
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Case 2

• 42 year old man presents with swollen, markedly
  inflamed. Knee tapped 3 days previous Dx gout.
  Then told MD By the way, I have von Willebrand
  disease. Put on colchicine with initial
  improvement, but then knee acutely worse retap
  showed frank blood.

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VON WILLEBRAND DISEASE

• Autosomal Dominant inheritance with variable
  penetrance
• Distinct variability in severity even within same
  family
• Lack of von Willebrand Factor causes
• Decreased Factor VIII Activity
• Defect in Platelet Adhesion

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VON WILLEBRAND DISEASEClassification

• Type I Quantitative Defect
• Type II Qualitative Defect
• Type IIa No multimer formation
• Type IIb Decreased multimers, decreased
  platelets
• Type IIc Other Protein Defects
• Type IIn Defect in Factor VIII Binding
• Type III Severe Quantitative Defect

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VON WILLEBRAND DISEASETreatment

• DDAVP Releases vWF from stores
• 70 respond must test prior to use in critical
  situation
• Humate-P Factor VIII concentrate rich in vWF
  approved for Rx of vWD
• Dosage 60-80 units/kg initial dose
• Cryoprecipitate Gold standard 40 units/kg for
  0-100 of normal ½ life 12-24 hours

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Case 3

• 28 year old woman, previously healthy, who comes
  in with sudden onset of petechial rash and heavy
  menses No medications. Platelet count in ER
  2,000/microliter Hgb 12.5 g/dl

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IMMUNE THROMBOCYTOPENIA PURPURA

• IgG mediated
• Platelets removed by macrophages
• Antibodies can act on marrow as well
• No good diagnostic test

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ITP

• Generally chronic illness in adults
• Patients often tolerate very low platelet counts
• AVOID PLATELET TRANSFUSIONS unless bleeding
  significantly
• If significant bleeding, need to be treated
  urgently

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ITP - Treatment

• Focus on inhibiting macrophage activity
• Corticosteroids
• High Dose IVIg
• IV Rhogam (anti-D) For Rh Positive patients
  only Causes mild hemolytic anemia
• Splenectomy For actively bleeding patients

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Case 4

• 56 year old woman s/p mitral valve replacement
  for 2nd time 2 hours ago on cardiopulmonary
  bypass 3½ hours now bleeding from chest tubes gt
  500 ml/hour, no clot formation in tubes. Blood
  pressure OK on low dose pressors has received 12
  units of platelets and 8 units of FFP, without
  effect

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DILUTIONAL COAGULOPATHYUsual Causes

• Post-operative bleeding, esp post-bypass
• Variceal bleeding
• Major trauma
• Aortic aneurysm
• Obstetrical emergencies

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DILUTIONAL COAGULOPATHY

• Generally need to lose 1½-2 blood volumes before
  invoking this
• Cannot tell bleeding from low platelets from
  bleeding from coagulopathy or from surgical
  bleeding
• Critical to determine cause before committing
  large amounts of blood products
• Treatment should be guided by lab results

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DILUTIONAL COAGULOPATHY

• Most important tests PT, Plt, Fibrinogen
• Goal is to correct to hemostatic values, NOT to
  normal
• Hemostatic values generally 30 of normal
  clotting factor levels
• PT lt 20-21 seconds
• aPTT lt 50 seconds
• Plt gt 50,000
• Fibrinogen gt 100

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DILUTIONAL COAGULOPATHY

• Products to use
• Platelets 6 units will raise count by 50,000
• FFP 4-6 units will raise all clotting factors
  by 25-30 (in normal sized adult)
• Cryoprecipitate 10 units will raise fibrinogen
  by 100 mg/dl
• 6 units FFP has fibrinogen of 12 units of
  cryoprecipitate
• GIVE PRODUCTS RAPIDLY!!!
• DDAVP usually not useful
• Amicar may be helpful if no evidence of DIC

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DILUTIONAL COAGULOPATHYSpecial Circumstances

• Aspirin May be able to use small doses of
  platelets
• Coumadin/Vitamin K deficiency Often need more
  FFP definitely need Vitamin K
• Heparin Reverse with protamine
• Uremia Cryoprecipitate will help improve
  platelet function
• IIb/IIIa inhibitors All platelets
  dysfunctional start with 12 units platelets
• Obstetrical emergencies DIC until proven
  otherwise correct fibrinogen early

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Case 5

• 48 year old man, Hx diabetes, hypertension, drug
  abuse, admitted with 3 days of fever confusion.
  Bloods in ER show Hgb 7.5 (normal 14.5 for him),
  platelets 12,000 Coombs negative. Blood smear
  shows schistocytes creatinine 1.6, LD 540, Bili
  4.5/0.8

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TTP

• Rare but important disease entity
• Sporadic relapsing form
• Caused by congenital defect of /or antibody
  against vWF-cleaving metalloproteinase
• Drugs also important
• Calcineurin inhibitors
• Ticlopidine/Clopidogrel
• Universally fatal without treatment
• With treatment gt 90 survival, usually without
  sequelae

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TTP

• Microangiopathic hemolytic anemia Blood smear
  is critical to assess
• Thrombocytopenia
• Mental status changes
• Fever
• Renal insufficiency
• DO NOT SEE coag abnormalities!

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TTP Differential Diagnosis

• DIC
• HUS
• Lupus vasculitis
• Malignant hypertension
• HEELLP syndrome (pregnancy only)
• Transplant rejection

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TTP - Treatment

• Corticosteroids
• Plasmapheresis/Plasma Exchange
• Easier to manage fluids
• Replaces missing metalloproteinase
• Removes antibody to metalloproteinase
• Vincristine, Splenectomy, Rituximab For
  refractory cases
• Aggressive 1.5-2 plasma volume exchanges daily
  sometimes need to continue x weeks
• Survival gt 90 sequelae minimal if begun early

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Case 6

• 65 year old man admitted with chest pain EKG
  shows non-Q wave MI, went to cath lab for cath
  stent placement. Post-procedure, echo shows LV
  thrombus in apex. Rx with Lovenox starting 5
  days later platelet count fell from 300,000 to
  35,000 over 1 day

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Heparin-Induced Thrombocytopenia

• Immunologic reaction
• Occurs 5-10 days post- initial exposure to
  heparin
• Usually not associated with bleeding
• 5-10 associated with thrombosis at presentation
• Of those without thrombosis, 50 will develop
  thrombosis within 14 days

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Heparin-Induced Thrombocytopenia

• Cause of thrombosis Platelet aggregation
• Coumadin alone, esp in large doses, runs risk of
  venous gangrene
• Need parenteral agent along with Coumadin
• Lepirudin Hirudin derivative
• Argatroban Small molecule thrombin inhibitor

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Case 7

• 75 year old woman, Hx paroxysmal A fib, fell
  suffered intertrochanteric fracture of L hip.
  Brought to ER _at_ 530 pm scheduled for surgery in
  AM aPTT 55 seconds. Only meds digoxin
  naproxen. No prior Hx of bleeding only has
  bruise over fractured hip

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ACQUIRED COAGULATION INHIBITORS Lupus
Anticoagulant

• Antiphospholipid antibody
• Laboratory rather than clinical anticoagulant
• Test by looking for presence of anticoagulant in
  assay where amount of phospholipid is
  rate-limiting step
• Causes prothrombotic rather than antithrombotic
  condition

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Case 8

• 92 year old woman brought to ER by family because
  of a large spontaneous ecchymosis on her R neck.
  Admission labs were normal except for an aPTT of
  70 seconds (normal 25-35 seconds)

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ACQUIRED COAGULATION INHIBITORS

• 80-90 are associated with hemophilia patients,
  mostly hemophilia A
• Most of the rest are associated with
  lymphoproliferative disorders
• Most commonly directed against factor VIII
• Typically low titer, high affinity, slow-binding
  antibodies, usually IgG
• Marked decrease in the survival of transfused
  product
• Commonly have MAJOR bleeding problems

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ACQUIRED COAGULATION INHIBITORS

• Test by mixing patients plasma with normal
  plasma, incubating x 1 hour _at_ 37, and then
  measuring the time it takes to clot. If time
  post-incubation is gt 5 seconds longer than the
  control time, ? presence of inhibitor to a
  clotting protein
• Then must determine the protein against which
  inhibitor is directed
• Occasionally have false positive lupus
  anticoagulant assays

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ACQUIRED COAGULATION INHIBITORS - Treatment

• Acute to stop bleeding
• FEIBA (Factor Eight Inhibitor Bypass Activity),
  or Autoplex 40 units/kg
• High Risk of Thromboembolic Disease
• Porcine Factor VIII
• Recombinant Factor VIIa Reserved for FEIBA
  failures and/or surgery
• Chronic To decrease antibody titer
• Steroids
• Rituximab
• Cyclophosphamide, Azathioprine
• Malmö Protocol (Induction of Immune Tolerance)
• 25-50 mortality even with optimal treatment