Bleeding and Thrombosis by leader6

VIEWS: 5 PAGES: 34

									Board Review

      6/11/2008
CLOTTING
 TESTS




           XII                        VII
                                       TF
                 VIII
                    IX                PL
             PL
                             X
                        V

                        II       PL


           Fibrinogen             Fibrin
                            MKSAP-Q1
• 80 yr man
• 3 week h/o massive bruising
• on no meds; FH negative
• Labs: platelets 350,000
         PT 12 sec; aPTT 78 sec; Bleeding time: 6 min
         fibrinogen 390 g/dL; D-dimer: 1000 ng/mL
         aPTT 1:1 mix: 71 sec
                                                  • acquired F VIII inhibitor
         LFTs normal
                                                  • DIC
                                                  • LA
                  Q: Dx?                          • Factor XII deficiency
                                                  • chronic liver disease
     Coag tests – MKSAP-Q2
 • 32 yr man; hematemesis x 2 h
 • Strict vegetarian diet x 4 weeks for weight control and
   abstained from alcohol for same period of time
 • PE: pale, spleen 3 cm enlarged; liver not palpable
 • Hbg 8.0; MCV 85; WBC 10; plts 75,000
 • PT 28 sec; aPTT 50 sec; BT 7.5 min; fibrinogen 165 mg/dL
 • Albumin 2.0; ASAT 75; ALAT 45
 • PT 1:1 mix: 12 sec; aPTT 1:1 mix: 30 sec

Q: Dx?
A: chronic liver disease
   (vitamin K deficiency; DIC; acquired f V inhibitor)
                      MKSA-Q3

• 46 yr man post CABG
• On heparin DVT prophylaxis 5000 U q 12
• Day 4 post-op right calf swelling and pain – Doppler-US: DVT
• plts 75,000


What do you do?
• Begin full-dose heparin
• Change to LMWH
• D/c heparin and observe
• D/c heparin and start warfarin
• D/c heparin, start danaproid or lepirudin
Heparin induced thrombocytopenia

 •   HIT (HIT-1, HIT-2, HAT)
 •   Platelet  of > 50 % from baseline
     after ≥ 5 days of heparin
     (earlier if heparin given within last 3 months)
     PLUS
 •   PT and aPTT normal
 •   Lab demonstration of heparin-dependent antibodies
     - HIT ELISA (PF4) or
     - HIPA test (heparin induced platelet aggregation test)



 •   Thromboses (arterial and venous)
                  LMWH and HIT




• HIT incidence: 2.7 % standard heparin vs. < 1 % LMWH
• but: 90-95 % cross-reactivity!
                              HIT
XII              VII




         X




      thrombin
                                                 [ASH 2001, Ortel]



                       Arixtra® = Fondaparinux

        clot
             Bleeding – MKSAP-Q4
• 55 yr woman
• Planned cholecystectomy
• Hx: easy bruising, frequent prolonged nosebleeds
• Bleeding after nasal surgery
• Blood count normal
• PT normal; aPTT 64 sec; aPTT 1:1 mix: complete correction
• XII 110 %; XI 16%; IX 98 %; VIII 112 %


     Q: How will you treat?

     A: FFP (Cryo; PCC; Amicar; nothing)
              Factor concentrates


• PCCs: II, VII, IX, X
  Bebulin®, FEIBA®, Autoplex®,
• Cryo: fibrinogen, von Willebrand factor (factor VIII)
• FFP: all other factors (little fibrinogen and von Willebrand factor)
         half-life of factor VII: 4 h
• Humate P: von Willebrand factor, factor VIII
               Bleeding – MKSAP-Q5
         • 30 yr man
         • Lifelong epistaxis + easy bruising
         • Tooth extraction – bleeding for several days
         • Adopted
         • Hbg 13.0; MCV 78; plts. 250,000
         • BT 13.5 min; PT 12 sec; aPTT 40 sec; TCT normal
         • Platelet aggregation study normal

Q: Dx?
A: von Willebrand’s disease
   (Glanzmann, mild hemophilia A or B, dysfibrinogenemia)
                    von Willeband’s disease
• Prevalence: 1 % of population
• Bruising – mucosal (nose, gums, menstrual, tonsillectomy, tooth extraction)

•   Dx:  von Willebrand factor activity
         factor VIII
         bleeding time, PFA100
        von Willebrand factor multimers
•   type 1: quantitative. 90 % of cases (all multimers present, but decreased)
•   type 2: qualitative (missing large multimers). 2A, 2B, 2N, platelet type
•   type 3: severe 1 (all multimers missing)

Rx:     type 1: DDAVP (0.3 g/kg) i.v., s.c., or intranasal
        type 2: Humate P (= factor VIII concentrate with vWf)
                 Cryo
              MKSAP-Q6




A 86   B 87     C 89     D 90   E 88
                        MKSAP-Q7
• 27 yr woman
• SLE
• 2 DVTs, now 3rd
• PT 13.6 sec; aPTT 43 sec; LA
• Standard heparin 5000 U bolus, then 1200 U/h. F/u aPTT 120 sec

Q: How to best give and monitor heparin rx?

 •  heparin
 • Use anti-Xa level, not aPTT
 • LMWH and follow aPTT
 • IVC filter
    Antiphospholipid antibodies

                    I) antibody test (ELISA)
     APL               • anticardiolipin
                       • anti-ß2-glycoprotein I
     A
L             ACA   II) functional test
A                      • lupus anticoagulant (inhibitor)




    ß2-GP I
                  Lupus anticoagulant

1) Screening test (aPTT, dRVVT, KCT, Silica clot time) – prolonged


2) Normal plasma mixing study – does not correct


3) Confirm (mix with excess of phospholipids) – corrects
    - hexagonal phospholipid test
    - platelet neutralization procedure (PNP)                XII                  VII
                                                                                   TF

                                                     aPTT                         PL
                                                                                        PT
                                                               PL
                                                                         X

                                                       DRVVT                 PL


                                                            Fibrinogen        Fibrin
                MKSAP-Q8
• 20 yr woman, bleeds after dental extraction
• SLE – steroids. No h/o bleeding; plts 160,000;
• PT 17.5 sec; corrects with 1:1 mix to 11.4 sec
• aPTT 43.3 sec; does not correct with 1:1 mix
• Fibrin (ogen) degradation products normal

Q: Cause of the prolonged prothrombin time?

• DIC
• Congenital XII deficiency
• F VIII inhibitor
• LA-hypoprothrombinemia syndrome
• Vitamin K deficiency
                      APLA syndrome

1) thrombosis or
2) recurrent abortions
3) pos. APLA test (repeat)

(+ thrombopenia, derm. or neurol. symptoms)



                                        Patient bleeds:
                                        • Hypoprothrombinemia
                                        • Low platelets
                         MKSAP-Q9

           • 33 yr man with CP
           • Coro: extensive 3 vessel disease
           • Non-smoker, normotensive, lipids including
             lipoprotein(a) normal
           • Strong FH of premature CAD and stroke

Q: Which thrombophilia test is most likely going to be abnormal?
           • Homocysteine
           • Factor V Leiden
           • Prothrombin 20210 mutation
           • Antiphospholipid antibodies
               MKSAP-Q10
 • 21 yr woman from Nigeria
 • SOB, CP post airline flight
 • On OCPs
 • Mother: thrombophlebitis x 2 postpartum.
 • Sister: sudden death pstpartum
 • VQ: PE

 Q: Which diagnostic study should be done next?

• Factor V Leiden and factor II 20210 gene studies
• Protein C, protein S, and antithrombin tests
• Screening tests for cancer, incl. Chest and abdo CT
• A lupus anticoagulant panel
              Thrombophilia
                              venous   arterial


Protein S deficiency           yes       yes


protein C def.                 yes       yes


AT III def.                    yes       yes


factor V Leiden                yes       no


prothrombin 20210              yes       no


homocysteinemia                yes       yes


MTHFR polymorphism             no        no


antiphospholipid antibodies    yes       yes
                 Factor V Leiden

•   prevalence : 2 - 15 % (western world)
•   RR for 1st DVT/PE:          heterozygotes: 3 - 8
                                homozygotes: 80
                                heterozygotes + pill: 30-50
•   Diagnosis: coagulation test (APC resistance) or genetic test


•   Not associated with arterial clots (except for selected patients)
Prothrombin 20210 polymorphism


  • prevalence: 2.3 % (normal population)
  • mild risk factor for 1st DVT/PE: RR 2.8
  • risk for recurrence of DVT/PE: not increased
  • associated with elevated prothrombin levels
  • not associated with arterial thrombosis
www.fvleiden.org
          MKSAP-Q11

• 47 year-old man
• DVT after 1 h airplane flight
• FH: uncle with DVT after hip arthroplasty,
       grandfather stroke age 68
• Thrombophilia w/u negative


Q: How long to anticoagulate?

A: 3 months (INR 2.0 – 3.0)
DVT/PE: Anticoagulation – how long?
1. after transient risk factors                      short (6 weeks - 3 mo)
2. Idiopathic DVT/PE:                                at least 3 months
    - Factor V Leiden, hetero                        at least 3 months
    - Prothrombin 20210 mutation:                    at least 3 months
    - Protein C or protein S deficiency              ???


   - ATIII deficiency:                               indefinite
   - homozygote factor V Leiden:                     indefinite
   - Factor V Leiden + prothrombin 20210 mutation:   indefinite
   - APLA syndrome:                                  indefinite
   - Tumor                                           indefinite (LMWH)
3. Recurrent DVT/PE                                  indefinite
                 MKSAP-Q12

   • 56 yr healthy man
   • DVT calf and popliteal vein
   • Adamantly refuses hospitalization



Q: Rx options?


A: LMWH s.c. in therapeutic doses + warfarin 5-10 mg qd
   (ASA, prophylactic LMWH, daily LMWH monitoring,
   15 mg warfarin)
                           MKSAP-Q13
 • 75 yr man
 • Calf and popliteal DVT after 10 h car ride
 • Smoking. Otherwise healthy
 • Phys. exam nl.
 • CBC, PT, PTT, routine serum chemistry nl

Q: What should be included in evaluation?

               1. Thorough PE and p.a. and lat. CXR
               2. Thorough PE, p.a. and lat. CXR, and chest/abdo MRI
               3. Thorough PE and p.a. and lat. CXR plus EGD/colonoscopy
               4. Thorough PE and CEA
                           MKSAP-Q14
 • 28 yr woman
 • ACA
 • three 1st trimester pregnancy losses
 • Now 6 weeks pregnant

Q: What is the most appropriate treatment?
                           MKSAP-Q14
 • 28 yr woman
 • ACA
 • three 1st trimester pregnancy losses
 • Now 6 weeks pregnant

Q: What is the most appropriate treatment?
                                          • Careful observation only
                                          • Prednisone 40 mg qd
                                          • Aspirin
                                          • IvIg infusions
                                          • Heparin and ASA
               MKSAP-Q15


• 35 yr woman
• epistaxis and bruising
• Plt: 5,000
• Refractory ITP (fails steroids)


Q: What therapy is best for long-term response?

A: splenectomy – (?Rituxan® = Rituximab?)
                                   ITP

• 1:20,000
• Antibodies against platelets, often against GPIIb/IIIa
• Dx: negative history, r/o all other causes:
    - iron studies (deficiency?)
    - vitamin B12, folate
    - blood smear (clumping?)
    - TSH (hypo?)
    - HIV
    (- ANA)
    - PT, PTT
    - bone marrow aspirate and biopsy: controversial
                           ITP - Therapy

• Guided by patient’s bleeding symptoms
• Treat when platelets < approx. 20 – 50,000 or when bleeding
• Prednisone 1 mg/kg
• Slow taper when platelet count > 50,000

• Iv Ig 1 g/kg q d x 2 d

• Anti-D antibody (WinRho) single dose. Response in 2-3 d. Duration of
  response: 1 month

• Relapse: splenectomy. Good response in 60-70%. Rituximab.

• If splenectomy fails: cyclophosphamide, azathioprine, danazol, multi-
  agent chemotherapy
Questions?
             Comments?

								
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