Bleeding Disorders Flashcards
What is the most common inherited bleeding disorder?
von Willebrand Disease
Petechiae, purpura or ecchymoses suggest what type of bleeding disorder?
thrombocytopenia
Enlarged spleen, liver or lymph nodes suggest what type of bleeding disorder?
chronic infections or malignancies
Telangiectasias suggest what type of bleeding disorder?
Osler-Weber-Rendu
Hyperextensible joints or paper-thin scars suggest what type of bleeding disorder?
Ehlers-Danlos
Skin plaques or scalloped tongue suggest what type of bleeding disorder?
amyloid
Musculoskeletal abnormalities suggest what type of bleeding disorder?
hemophilia
What is the mutation seen in vWD?
quantitative or qualitative deficiency of von Willebrand factor
What clinical symptoms is characteristic of vWD?
mucocutaneous bleeding
What is the function of vWF?
carrier protein for factor VIII
ligand to bind GPIB receptor on platelets for initiation of platelet adhesion to damaged blood vessel
Where is vWF made?
endothelial cells & megakaryocytes
Where is Factor VIII produced?
liver & kidney
What are the 3 main types of vWD?
Which type is most common?
-
Type 1 - MC (80%)
- heterozygous or partial quantitative deficiency vWF
- mild disease
-
Type 2
- abnormal vWF produced
- variable severity
-
Type 3
- homozygous
- absent or severe deficiency vWF
- plasma levels factor VIII severely decreased
- clinically looks like hemophilia A
How do the different types of vWD in the multimer analysis?
- Type 1: all multimes, but reduced quantity
- Type 2: variable
- Type 3: none
What is the cause of Hemophilia A?
What are the different severities?
deficiency of factor VIII
severe <1%
moderate 1-5%
mild >5%
Hemophilia A has what type of inheritance pattern?
X-linked recessive
What are the clinical symptoms of a patient with Hemophilia A?
bleeding into joints
hemophilic arthropathy
bleeds with minor trauma
NO mucocutaneous bleeding
What lab values would you expect to see in a patient with Hemophilia A?
- prolonged PTT
- complete correction with mixing study
- genetic testing - prenatal testing
- normal PT, TT & bleeding time
- extrinsic & common pathway are in tact
- platelet function & vascular integrity are also in tact
What is the treatment for Hemophilia A?
DDAVP mild cases
factor VIII concentration moderate to severe disease
What are possible complications to treatment of Hemophilia A?
inhibitors factor VIII
HIV, Hepatitis, Parvovirus B19 (b/c acquired form transfusion)
What is the mutation in Hemophilia B?
It has what type of inheritance pattern?
deficiency factor IX
X-linked recessive
What is the most common cause of acquired factor deficiency?
Liver disease
Vitamin K is required for function of what factors?
factors
II, VII, IX, X
protein C & protein S
Normal hemostasis has what 3 components?
- vascular wall integrity
- Platelets (adequate # & function)
- coagulation cascade
What is Virchow’s Triad?
alone or in combo predisposes to thrombosis
- Endothelial injury
- Hypercoaguability
- Abnormal blood flow
What situations would warrant a complete thrombophilia workup?
thromboembolic event under age 50
unprovoked event at any age
What mutation causes Factor V Leiden?
point mutation factor V that makes it resistant to proteolytic action of activated protein C
protein C normally degrades activated factor V & factor VIII
What is the most common hereditary predisposition to venous thrombosis?
Factor V Leiden
Individuals homozygous for Factor V Leiden have what relative risk of developing venous thrombosis?
80x
Prothrombin gene mutation is associated with what molecular abnormality?
elevated levels of prothrombin & subsequent increased risk of thrombosis
increased levels TAFI- protein that inhibits clot lysis, so clots last longer
Factor VIII levels what percent of normal are associated with increased risk of venous & arterial thrombosis?
This is often seen in what situation?
150%
inflammatory states (acute phase reactant)
What are the 3 common risk factors for venous thromboembolism?
factor V Leiden
prothrombin gene mutation
elevated factor VIII
What test do you perform if you suspect Factor V Leiden?
screen: activated protein C resistance
genetic testing is definitive
Deficiency in Protein C increases risk of DVT in what specific locations?
legs & mesenteric veins
pulmonary embolism
Protein C & Protein S deficiency are associated with what warfarin-related issue?
warfarin-induced skin necrosis
What is the clinical presentation of neonates with severely decreased levels of protein C?
DIC
purpura fulminans neonatorum
What are acquired increases in protein C that may mask deficiencies?
ischemic heart disease
pregnancy
post-menopausal state
hormone replacement therapy
oral contraceptives
Patients with deficiencies in protein C, protein S & antithrombin often have a thromboembolic even before what age?
45
How long after a thrombotic event should you wait before thrombophilia testing?
2 weeks
What thrombophilia tests are not affected by anticoagulants or active thrombosis?
- activated protein C resistance (APCR)
- homocysteine
- anticardiolipin antibodies
- genetic tests for V leiden and prothrombin gene
What factors predispose to venous thrombosis?
- factor V Leiden
- prothrombin mutation
- elevated VIII levels
- increased levels II, IX, XI
- deficiencies protein C, S
What factors predispose to arterial thrombosis?
- heparin platelet antibodies
- hyperhomocysteinemia
- antiphospholipid antibodies
- elevated levels factor I, V, VII, vWF
- deficiency antithrombin
