Flashcards in Fung: Coagulation II Deck (53):
Clinically, most bleeding disorders can be divided into these two categories...
In this type of bleeding disorder, petechiae and mucosal bleeding are rare, but hemarthroses, deep hematomas and delayed bleeding are common; seen in males
coagulation type bleeding disorder
In this type of bleeding disorder, petechiae and mucosal bleeding are common, but hemarthroses, deep hematomas and delayed bleeding are RARE; seen in females
platelet type bleeding disorder
This is the most common inherited bleeding disorder; it is a defect in PLATELET ADHESION; combined platelet and coagulation defect; 4 main types
von Willebrand disease
Where is von Willebrand factor synthesized? Where is it sotred? What does it do?
synthesized in endothelial cells and megakaryocytes; stored in Weibel-Palade bodies of endothelial cells and alpha granules of megakaryocytes; mediates platelet adhesion by binding GPIb
Another name for von Willebrand factor
What does vWF complex with in the circulation to decrease its degradation?
Most common type and results in a mild bleeding disorder
QUANTITATIVE disorder showing reduced amounts of vWF
Laboratory evaluation will show
Prolonged PTT and BT
Decreased vWF and activity
von Willebrand disease: Type 1
Qualitative (functional) defect of vWF
IIM – rare defect that prevents vWF binding to GPIb
IIN – rare defect with reduced vWF binding to FVIII
von Willebrand disease: Type 2
What is the main difference between von Willebrand disease type IIa and type IIb?
IIa: absence of high molecular weight multimers, ristocetin cofactor (vWF) activity decreased;
IIb: decreased high molecular weight multimers, enhanced ristocetin cofactor, DO NOT give DDAVP
Defect of platelet adhesion
Due to decreased platelet GPIb/V/IX
Patients clinically manifest with thrombocytopenia and giant platelets
PFT: aggregation on all agonists except ristocetin
Similar picture to vWD on PFT
Peripheral smear will show large platelets (unlike vWD)
Bernard Soulier syndrome
In Bernard Soulier syndrome, platelet adhesion is defective due to a decrease in (blank)
How can you differentiate von Willebrand disease from Bernard Soulier syndrome?
Bernard Soulier syndrome - giant platelets
Autosomal recessive disorder due to deficient GP IIb/IIIa (fibrinogen receptor)
Platelets lack the PLA1 antigen
PFT: fail to aggregate with all agonists but ristocetin
What is deficient in Glanzmann thromasthenia?
GP IIb/IIIa (fibrinogen receptor)
**platelets don't have PLA1 antigen
You can also have defects in granules of platelets. In alpha granule disease, aggregation is blunted with all agents except (blank)
**one of the components of dense granules
**associated with gray-platelet syndrome
If you have dense granule disease, you will not get a (blank)
second wave of aggregation
These two drugs can cause excessive bleeding by inhibiting COX-1 (the enzyme involved in thromboxane A2 production)
**by blocking this enzyme, you will not get dense granule release and the secondary wave of aggregation
Which has a reversible effect, aspririn or NSAIDs?
What are these?
Immune thrombocytopenic purpura (ITP)
Thrombotic thrombocytopenic purpura (TTP)
Hemolytic uremic syndrome (HUS)
Heparin induced thrombocytopenia (HIT)
disorders characterized by thrombocytopenia (low platelets)
Diagnosis of exclusion: healthy patient with isolated thrombocytopenia with no other obvious cause
Antigenic target of the antibody varies
immune thrombocytopenic purpura
**when there is no other cause for the thrombocytopenia, consider this
Syndrome resulting from widespread formation of microvascular platelet thrombi affecting
Central nervous system
thrombotic thrombocytopenic purpura
What are some of the symptoms expressed in TTP?
microangiopathic hemolytic anemia
In thrombotic thrombocytopenic purpura, there is an acute deficiency in vWF-cleaving metalloprotease. What does this lead to?
an accumulation of ultra-large vWF multimers which bind platelets and lead to thrombi in the microvasculature and thrombocytopenia
Thrombotic microangiopathy characterized by
Acute renal failure
Microangiopathic hemolytic anemia
Most commonly associated with bloody-diarrhea caused by shiga-toxin producing bacteria (E. coli O157:H7 or S. dysenteriae)
Hemolytic uremic syndrome
Hemolytic uremic syndrome is most commonly associated with what??
shiga toxin producing bacteria (like E. coli O157:H7 or S. dysenteriae)
**causes bloody diarrhea
Occurs in 1-3% of patients treated with unfractionated heparin for greater than 5 days
heparin induced thrombocytopenia
Heparin induced thrombocytopenia is an immune mediated disorder caused by (blank) antibodies against the complex of heparin and PF4
Which is more common in heparin induced thrombocytopenia, bleeding or thrombosis?
3 symptoms of herparin induced thrombocytopenia?
Hemophilia A is a congenital X-linked recessive deficiency in (blank), which results in absent circulating (blank) and lifelong bleeding
factor 8; factor 8
How do patients with hemophilia A present?
with delayed bleeding
joint and muscle bleeding
What will the following values be like in hemophilia A?
normal platelet count, PT and TT
Hemophilia B is due to a congenital X-linked recessive deficiency in (blank), which results in decreased or absent (blank) and lifelong bleeding
factor 9; factor 9
How does hemophilia B present?
clinically identical to hemophilia A - delayed bleeding, joint and muscle bleeding
prolonged PTT, normal PT, TT
Liver disease can cause this...
decreased synthesis of most clotting factors, including fibrinogen
chronic DIC due to impaired clearance of D-dimer
Vit K deficiency leads to impaired production of Vit K dependent clotting factors. What are they?
List 4 things that can cause Vit K deficiency
hemorrhagic disease of the newborn **newborns get a shot of Vit K to avoid this
antibiotics **knocks out gut flora, so decreased Vit K absorption
Acquired syndrome characterized by the intravascular activation of coagulation
disseminated intravascular coagulation
Causes of disseminated intravascular coagulation?
endotoxin causing sepsis
In DIC, the patient will have prolonged exposure to (blank) resulting in generalized activation of the coag system and thrombin generation. In addition, there will be no activation of (blank)
tissue factor; tissue factor pathway inhibitor
What do fibrin formation and fibrinolysis cause in DIC?
microthrombi and consumption of clotting factors and platelets
Possible clinical manifestations in DIC
What does the differential diagnosis of thrombophilia depend on?
the type of thrombosis (arterial or venous)
Inherited autosomal dominant condition responsible for 50% of the cases of hereditary thrombophilia
Due to a point mutation in the FV gene that makes FV Leiden resistant to proteolytic cleavage by APC
Heterozygotes have 5-10 increased risk of thrombosis
Activated protein C resistance
What does activated protein C (APC) do? In activated protein C resistance (APCR), what is the problem?
Activated protein C usu degrades factor 5a and 8a; if these cannot be degraded, may lead to longer duration of thrombin generation and increased risk of thrombosis
Autosomal dominant disorder characterized by recurrent venous thrombosis
No inactivation of Factors II, IXa, Xa, XIa, XIIa
Heterozygotes have 5-10 increased risk of thrombosis
Homozygosity is considered incompatible with life
What is the problem in anti-thrombin deficiency?
no inactivation of factors II, 9a, 10a, 11a, and 12a which leads to recurrent venous thrombosis
An autoimmune thrombophilic condition in which patients have circulating antibodies against plasma proteins that bind to phospholipids
Recurrent arterial and venous thrombosis
What are some things that you might form antibodies to in antiphospholipid syndrome?
What is the difference between primary and secondary antiphospholipid syndrome?
primary APL: healthy individuals
secondary APL: associated w disease (lupus, HIV, cancers, drugs)
Autosomal dominant condition due to a point mutation in the prothrombin gene
Mutation enhances prothrombin gene transcription leading to elevated levels of prothrombin
Second most common cause of inherited thrombophilia
prothrombin variant (G20210A)