Hematology8-25

Question 1

Your patient is a 24 year old female who presents to your office to establish care. Upon questioning she tells you that she had frequent nosebleeds as a child and has had heavy menstrual periods since menarche. Are these elements of her medical history significant?

Answer 1

Yes, she may have von Willebrand factor deficiency.

Clinical manifestation:
1. Life-long Hx of gingival bleeding, epistaxis and/or menorrhagia

Question 2

What do you expect the lab values to show in a patient with von Willebrand disease?

Answer 2

1. Normal platelet levels
2. Prolonged bleeding time (platelets present have impaired functioning)

Question 3

Diagnosis:

Your patient presents with ecchymoses, petechiae and mucosal bleeding, but lacks any other cause of thrombocytopenia…

Answer 3

This presentation should always be suscpicious for auto immune platelet destruction. (i.e. immune thrombocytopenic purpura)

Question 4

This molecule promotes platelet adhesions AND acts as a protective carrier protein for circulating factor VIII.

Answer 4

von Willebrand factor

Question 5

What is the most common cause of inherited thrombophilia?

Answer 5

Factor V Leiden

1-9% of Caucasian populations are heterozygote carriers.

Question 6

MA:

How does protein C prevent coagulation?

Answer 6

Protein C degrades Factor Va and Factor VIIIa. Proteolytic inactivation of Va prevents the conversion of prothrombin to thrombin.

Question 7

What are the major clinical complications of Factor V Leiden?

Answer 7

1. DVT–> leads to pulmonary thromboembolism if untreated
2. Cerebral vein thrombosis
3. recurent pregnancy loss

Note, a heterozygous indiviudal has a 5-10x greater risk for DVT. A homozygous individual has a 50-100X greater risk for DVT.

Question 8

Diagnosis:

Coagulation assay for a patient with end-stage renal disease

Answer 8

PT: normal
aPTT: normal
Platelet count: normal
Bleeding time: increased

This is a qualitative platelete disorder. The platelet count is normal. ESRD –> uremia –>uremic toxins impair platelet aggregation and adhesion

Question 9

Which coagulation pathway is affected by warfarin?

Answer 9

Extrinsic coagulation (PT)

Actually, warfarin will increase the PT and the aPTT; however, its affects on PT are more significant. Remember, you are your EX are at WAR(farin)!

Question 10

Which coagulation pathway is affected by heparin?

Answer 10

Intrinsic coagulation (aPTT)

HI!

Question 11

Pathogenesis:

Thalassemia intermedia

Answer 11

Mutation in the Kozac sequence, which is 3 bases upstream from the start codon on mRNA.

Guanine –> cytosine mutation

Question 12

Which protein is mutated in patients with polycythemia vera?

Answer 12

JAK2, the cytoplasmic tyrosine kinase

Be sure not to confuse this with receptor tyrosine kinases which have intrinsic tyrosine kinase activity.

Question 13

Which fibrinolytics are fibrin specific?

Answer 13

1. tissue plasminogen activator (tPA)
2. reteplase
3. tenecteplase

Question 14

Which fibrinolytics are nonfibrin-specific?

Answer 14

1. streptokinase

Question 15

What is the difference in mechanism of action between fibrin specific and nonfibrin-specific fibrinolytics?

Answer 15

Fibrin specific fibrinolytics bind ONLY to recently formed clots and are associated with less systemic activation of plasmin. Fibrin specific drugs have a decreased risk of bleeding.

Question 16

What is the function of plasmin?

Answer 16

Plasmin degrades (1) fibriniogen and (2) fibrin clots

Question 17

What is the function of plasminogen?

Answer 17

Plasminogen is a plasmin precursor

Question 18

What is the function of thrombin?

Answer 18

Thrombin converts fibrinogen into a fibrin clot.

Question 19

List the five (5) contraindications of fibrinolytic usage.

Answer 19

1. hemorrhagic stroke
2. Hx of ischemic stroke in the last year
3. active internal bleeding
4. BP higher than 180/110 mmHg
5. suspected dissecting aneurysm

Question 20

Your patient has leukocytosis. In order to differentiate chronic myelogenous leukemia from a leukemoid reaction, what would you expect of the leukocyte alkaline phosphatase score?

Answer 20

CML: Low leukocyte alkaline phosphatase
Leukemoid reaction: Elevated to normal alkaline phosphatase

*LAP is an enzyme released from neutrophils. In CML the leukocytes are abnormal so they lack this enzyme; however, in leukemoid reactions there are excess WBCs, so there may be an increase in LAP.

Question 21

Diagnosis:

Your patient is a 7-year-old male who presents with:
(1) arthralgia
(2) abdominal pain
(3) lower extremity purpura
(4) renal involvment

Answer 21

This is textbook Henoch-Schonlein purpura.

Question 22

Diagnosis:

9-year-old female with
(1)prolonged Bleeding time
(2)prolonged PTT

Answer 22

von Willebrand disease

von Willebrand disease is due to a functional defect in platelets (prolonged bleeding time) and Factor VIII (intrinsic pathway/PTT).

Question 23

Clinical Manifestation:

Sickle cell trait

Answer 23

1. generally asymptomatic
2. hematuria (sometimes)
3. inability to concentrate urine (sometimes)
4. UTI (high altitudes)
5. splenic infarction (high altitudes)

Question 24

Why is desmopressin used to treat mild-to-moderate hemophilia A?

Answer 24

It realeases vWF and Factor VIII from the endothelium. Desmopressin is a vasopressin analog.

Question 25

TTP vs. DIC
(1) Patients bleed
(2) Coagulation cascade is activated
(3) PT and PTT are prolonged
(4) Low fibrinogen and increased fibrin degradation products (FDP)

Answer 25

DIC

Thrombocytopenic purpura (TTP) has activated platelets. There is no bleeding and PT, PTT and FDP are all normal.

Question 26

List the three (3) chronic myeloproliferative disorders.

Answer 26

1. Polycythemia vera
2. Essential thrombocytosis
3. Primary myelofibrosis