6.17.09 Moll Heme Board Review

7/28/2019 6.17.09 Moll Heme Board Review

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Board Review

6/17/2009


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CLOTTINGTESTS

Fibrinogen

VII

TFXII

X

Fibrin

PLPL

PLV

II

VIII

IX


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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

LFTs normal

Q: Dx?

acquired F VIII inhibitor

DIC

LA

Factor XII deficiency

chronic liver disease

acquired F VIII inhibitor

DIC

LA

Factor XII deficiency

chronic liver disease


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Coag testsMKSAP-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)


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Heparin induced thrombocytopenia

HIT (HIT-1, HIT-2, HAT)

Platelet of> 50 % from baselineafter 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)


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LMWH and HIT

HIT incidence: 2.7 % standard heparin vs. < 1 % LMWH

but: 90-95 %cross-reactivity!


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HIT

[ASH 2001, O

clot

X

XII VII

thrombin

Arixtra = Fondaparinux


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BleedingMKSAP-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)


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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


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BleedingMKSAP-Q5

30 yr man

Lifelong epistaxis + easy bruising

Tooth extractionbleeding 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 Willebrands disease

(Glanzmann, mild hemophilia A or B, dysfibrinogenemia)


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von Willebands disease

Prevalence: 1 % of population

Bruisingmucosal (nose, gums, menstrual, tonsillectomy, tooth extraction)

Dx: von Willebrand factor activity factor VIII bleeding time, PFA100von 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 intranasaltype 2: Humate P (= factor VIII concentrate with vWf)

Cryo


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MKSAP-Q6

A 86 B 87 E 88C 89 D 90


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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

heparin

Use anti-Xa level, not aPTT

LMWH and follow aPTT

IVC filter


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Antiphospholipid antibodies

APL

A

ACALA

I) antibody test (ELISA)

anticardiolipin

anti-2-glycoprotein I

II) functional test lupus anticoagulant (inhibitor

2-GP I


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Lupus anticoagulant

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

2) Normal plasma mixing studydoes not correct

3) Confirm (mix with excess of phospholipids)corrects

- hexagonal phospholipid test

- platelet neutralization procedure (PNP)

Fibrinogen

VIITF

XII

X

Fibrin

PPLPL

PLDRVVT

aPTT


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MKSAP-Q8

20 yr woman, bleeds after dental extraction

SLEsteroids. 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

DIC

Congenital XII deficiency

F VIII inhibitor

LA-hypoprothrombinemia syndrome

Vitamin K deficiency


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APLA syndrome

1) thrombosis or

2) recurrent abortions

3) pos. APLA test (repeat)

(+ thrombopenia, derm. or neurol. symptoms)

Patient bleeds:

Hypoprothrombinemia

Low platelets


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MKSAP-Q9

Homocysteine

Factor V Leiden

Prothrombin 20210 mutation


Q: Which thrombophilia test is most likely going to be abnormal?

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

Homocysteine

Factor V Leiden

Prothrombin 20210 mutation



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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

Thrombophilia


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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)


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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


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www.fvleiden.org


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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 2.03.0)


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DVT/PE: Anticoagulationhow 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


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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)


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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/colonoscop

4. Thorough PE and CEA

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/colonoscop

4. Thorough PE and CEA


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MKSAP-Q14

28 yr woman

ACA

three 1st trimester pregnancy losses

Now 6 weeks pregnant

Q: What is the most appropriate treatment?


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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

Careful observation only

Prednisone 40 mg qd

Aspirin IvIg infusions

Heparin and ASA


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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?)


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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


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ITP - Therapy

Guided by patients bleeding symptoms

Treat when platelets < approx. 2050,000 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


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6.17.09 Moll Heme Board Review