Hemostasis and Bleeding Disorders

Question 1

Factors in PTT Pathway

Answer 1

Intrinsic Pathway: Contact factors, XII, XI, IX, VIII

Question 2

Factors in PT Pathway

Answer 2

EXTRINSIC Pathway: VII, tissue Factor

Question 3

Common Pathway factors

Answer 3

X, V, Prothrombin (II), Thrombin (IIa), Fibrinogen (I), Fibrin (Ia)

Question 4

Confirming Heparin contamination

Answer 4

prolonged PTT

1) check from direct venipuncture
2) Prolonged Thrombin Time, normal reptilase time.

Question 5

Etiologies for isolated elevation in PT

Answer 5

Vit K def, Liver Insufficiency, poor nutrition, coumadin, factor VII def/inhibitor

Question 6

two factor deficiencies which lead to very elevated PTT but no bleeding phenotype

Answer 6

HMWK and Factor XII

Question 7

Patient comes in with bleed and prolonged PT. PT does not correct with mixing study. Lupus inhibitor is detected but patient is bleeding. What factor inhibitor is most likely present?

Answer 7

Factor II, Prothrombin

Question 8

What does thrombin time measure?

What causes prolongation?

Answer 8

Conversion of fibrinogen to fibrin
Prolonged by heparin contamination (reptilase time normal) and Hypofibrinogenemia and dysfibrinogenemia (reptilase time prolonged)

Question 9

PFA 100 test is performed in bleeding patient

1) what can cause false positive?
2) Col/Epi closure time is prolonged, Col/ADP time is normal. What is cause?
3) Col/Epi closure time is prolonged, Col/ADP time is prolonged. What is cause?

Answer 9

1) Anemia (HCT <28%), TCP (<100k)
2) Aspirin
3) VWD, Platelet defect, renal failure, BSD, Glanzmann’s

Question 10

RIPA Study:
Normal- ADP, Collagen
No Response- Ristocetin
Giant platelets

Answer 10

Bernard Soulier

Question 11

RIPA Study:
Normal- Ristocetin
Absent- ADP, Collagen
Normal Appearing Platelets

Answer 11

Glanzmann’s Thrombasthenia

Question 12

RIPA Study-
Normal- Primary Wave with ADP, Collagen, Ristocetin
Blunted Secondary Wave
Abnormal Appearing platelets

Answer 12

Storage Pool Disease (like Grey Platelet syndrome)

Question 13

RIPA Study:
Normal Primary ADP wave, Ristocetin
Blunted- secondary wave and response to collagen
Normal Platelet morphology

Answer 13

NSAID/ASA effect

Question 14

Testing for Factor XIII def

Answer 14

Clot stability assay. Dissolution of clot in less than 24 hours by 5FU-Urea is consistent with factor XIII def

Question 15

Normal PT, prolonged PTT, normal platelet count

VWF antigen low (20%), VWF:Rco activity normal, multimers normal, RIPA normal, low factor VIII activity

Answer 15

Type I VWD

Question 16

Normal PT, Elevated PTT, normal platelet count

Low VWF antigen but lower VWF activity. No large VWF multimers, low FVIII activity, normal RIPA

Answer 16

Type IIa VWD

Question 17

Normal PT, Prolonged PTT, decreased VWF antigen and activity, decreased large VWF multimers but increased ripa and low platelets

Answer 17

Type IIB VWD

don’t give DDAVP

Question 18

Normal PT, Prolonged PTT, Decreased VWF antigen, pronounced drop in activity, normal multimers, decreased FVIII activity, normal RIPA, normal platelet count

Answer 18

Type IIM VWD

Question 19

Normal PT, Elevated PTT, normal VWF Antigen and activity. Normal Multimers, very low FVIII level, normal RIPA, normal platelet count. Female patient

Answer 19

Type IIN VWD

Test VWF binding affinity to normal FVIII, will be low in this disease

Question 20

Normal PT, Elevated PTT, extremely low VWF antigen and activity, complete absnce of large VWF multimers, decreased FVIII, normal platelets, normal RIPA

Answer 20

Type III VWD

Question 21

47 yo man who just had CT surgery using fibrin glue. Post op he starts bleeding and PT/PTT are prolonged and don’t correct on mixing study.

Answer 21

FV inhibitor

Fibrin glue contains bovine FV which can lead to alloantibodies

Question 22

Goal FVIII or IX level for:
Minor surgery-> _____% for _____ days
Major Surgery-> _____% for _____ days

Answer 22

Minor-> 50% x 3-5 days

Major-> 80% x 10-14 days

Question 23

Newborn with delayed umbilical cord stump bleeding. Normal PT/PTT, normal platelet count
Diagnosis:
Confirmatory Lab:
Treatment:

Answer 23

Diagnosis: Factor XIII def
Lab: 5M urea clot lysis time (<24h)
Treatment: rFXIII (Tretten)

Question 24

Child with easy bruising, oozing blood on heel stick
Normal PT/PTT, normal fibrinogen, VWF scree, platelet count, factor XIII level.

Platelet agg shows aggregation to ristocetin only
Diagnosis:
Pathophys:

Answer 24

Diagnosis: Glanzmann’s Thrombasthenia
Pathophys: deficiency of platelet GPIIb/IIIa receptor (diagnosed by flow cytometry)

treated with platelet transfusion and novoseven

Question 25

Child with several months of easy bruising.
Normal PT/PTT, normal fibrinogen, VWF scree, platelet count, factor XIII level. Enlarged platelets noted

Platelet agg shows aggregation to ADP and collagen but no activity with Ristocetin

Diagnosis:
Pathophys:

Answer 25

Diagnosis:Bernard Soulier Disease
Pathophys: Deficiency of platelet GPIb receptor

Treatment with platelet transfusions and novoseven

Question 26

How do you tell the difference between Glanzmann’s Thrombasthenia and Congenital Afibinogenemia?

Answer 26

Congenital Afibrinogenemia will have prolonged PT, PTT, and TT.
Both have same RIPA pattern (Normal with ristocetin but absent with collagen/ADP)

Question 27

15 yo presents with recurrent nosebleeds. Normal PT, PTT. Thrombocytopenia. Platelets appear grey. Which platelet granules are missing?

Answer 27

alpha granule

Abnormal aggregation with collagen

Question 28

15 yo Puerto Rican boy with albinism presents with recurrent epistaxis. Normal PT/PTT but low platelet agg with ADP. Second wave on platelet agg is completely absent with ADP and Epi
Diagnosis->
Gene Defect->

Answer 28

Dense Granule Deficiency. Defect in HPS-1 gene

Question 29

23 yo woman with epistaxis and gume bleeding since childhood. Normal coag profile but abnormal aggregation of platelets with epinephrine.
Diagnosis:
Pathophys:

Answer 29

Diagnosis: Quebec Platelet D/o
Pathophys: increased Urokinase-type plasminogen activator