Hematology8-25 Flashcards
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?
Yes, she may have von Willebrand factor deficiency.
Clinical manifestation:
1. Life-long Hx of gingival bleeding, epistaxis and/or menorrhagia
What do you expect the lab values to show in a patient with von Willebrand disease?
- Normal platelet levels
- Prolonged bleeding time (platelets present have impaired functioning)
Diagnosis:
Your patient presents with ecchymoses, petechiae and mucosal bleeding, but lacks any other cause of thrombocytopenia…
This presentation should always be suscpicious for auto immune platelet destruction. (i.e. immune thrombocytopenic purpura)
This molecule promotes platelet adhesions AND acts as a protective carrier protein for circulating factor VIII.
von Willebrand factor
What is the most common cause of inherited thrombophilia?
Factor V Leiden
1-9% of Caucasian populations are heterozygote carriers.
MA:
How does protein C prevent coagulation?
Protein C degrades Factor Va and Factor VIIIa. Proteolytic inactivation of Va prevents the conversion of prothrombin to thrombin.
What are the major clinical complications of Factor V Leiden?
- DVT–> leads to pulmonary thromboembolism if untreated
- Cerebral vein thrombosis
- 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.
Diagnosis:
Coagulation assay for a patient with end-stage renal disease
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
Which coagulation pathway is affected by warfarin?
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)!
Which coagulation pathway is affected by heparin?
Intrinsic coagulation (aPTT)
HI!
Pathogenesis:
Thalassemia intermedia
Mutation in the Kozac sequence, which is 3 bases upstream from the start codon on mRNA.
Guanine –> cytosine mutation
Which protein is mutated in patients with polycythemia vera?
JAK2, the cytoplasmic tyrosine kinase
Be sure not to confuse this with receptor tyrosine kinases which have intrinsic tyrosine kinase activity.
Which fibrinolytics are fibrin specific?
- tissue plasminogen activator (tPA)
- reteplase
- tenecteplase
Which fibrinolytics are nonfibrin-specific?
- streptokinase
What is the difference in mechanism of action between fibrin specific and nonfibrin-specific fibrinolytics?
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.
What is the function of plasmin?
Plasmin degrades (1) fibriniogen and (2) fibrin clots
What is the function of plasminogen?
Plasminogen is a plasmin precursor
What is the function of thrombin?
Thrombin converts fibrinogen into a fibrin clot.
List the five (5) contraindications of fibrinolytic usage.
- hemorrhagic stroke
- Hx of ischemic stroke in the last year
- active internal bleeding
- BP higher than 180/110 mmHg
- suspected dissecting aneurysm
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?
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.
Diagnosis:
Your patient is a 7-year-old male who presents with:
(1) arthralgia
(2) abdominal pain
(3) lower extremity purpura
(4) renal involvment
This is textbook Henoch-Schonlein purpura.
Diagnosis:
9-year-old female with
(1)prolonged Bleeding time
(2)prolonged PTT
von Willebrand disease
von Willebrand disease is due to a functional defect in platelets (prolonged bleeding time) and Factor VIII (intrinsic pathway/PTT).
Clinical Manifestation:
Sickle cell trait
- generally asymptomatic
- hematuria (sometimes)
- inability to concentrate urine (sometimes)
- UTI (high altitudes)
- splenic infarction (high altitudes)
Why is desmopressin used to treat mild-to-moderate hemophilia A?
It realeases vWF and Factor VIII from the endothelium. Desmopressin is a vasopressin analog.
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)
DIC
Thrombocytopenic purpura (TTP) has activated platelets. There is no bleeding and PT, PTT and FDP are all normal.
List the three (3) chronic myeloproliferative disorders.
- Polycythemia vera
- Essential thrombocytosis
- Primary myelofibrosis
