Clinical Conditions Associated with Abnormal Hemostasis Flashcards
how common is Von Willebrands Disease?
most common inherited bleeding disorder in North America
1-2% of general population
how do you get Von Willebrand’s Disease?
autosomal trait
recessive trait
what does Von Willebrand’s Factor do?
- mediate platelet adhesion at sites of vascular injury
- binds to and protects Factor VIII from in-vivo proteolysis (the breakdown of protein into amino acids)
deficiency of VWFactor affects
primary hemostasis
what percentage is a mild form of deficiency of VWFactor
> 40% VWF
deficiency of VWFactor is associated with
mucosal bleeding
- epistaxis
- menorrhagia
- bruising
- oral cavity
- GI bleeding
more severe forms of of deficiency of VWFactor
- decrease VWF and decrease Factor VIII
- severe mucosal bleeding
- bleeding into joints and muscles
forms of severe deficiency of Factor VIII
- spontaneous joint bleeds
- retoperitoneal hemorrhage (behind peritoneal: spleen, spine, part of aorta)
- resembles hemophilia
treatment of for deficiency of VWF/Factor VIII
DDAVP (in mild cases): Desmopressin, Stimulating release of the VWF from its storage sites in endothelial cells. Cleaving the large VWF multimers circulating in plasma into smaller multimers.
- plasma products that contain VWF
- adjunct treatments such as anti-fibrinolytic (Amicar) and estrogen
what are some plasma products that contain VWF
- cryoppt
- FVIII/VWF concentrates
- purified VWF
what are congenital plasma coagulation deficiencies
- hemophilia A & B (Factor VIII and IX deficiency)
- Factors XI, X, V, II and I (Fibrinogen)
how is Hemophilia A & B acquired?
- X-linked recessive disorders (woman carries it)
Severity of bleeding for hemophilia A and B
factory activity level
- <1% activity - spontaneous bleeds
- 1-5 % - post-operative and bleeding with minor trauma
- 6-20% - post-operative and with trauma
treatment hemophilia A and B
- replacement with specific factor concentrates
- avoid platelet inhibitory drugs
treatment for Factor XI, X, V, II and I (Fibrinogen) deficiencies
- replacement transfusion with FFP
- no platelet inhibitory drugs
Congenital Plasma Coagulation Deficiencies NOT associated with abnormal bleeding
- Factor XII deficiency (ex: Hageman - intrinsic not really activated)
- HMW Kininogen Deficiency (Fitzgerald Factor)
- Prekallikrein Deficiency (Fletcher Factor)
Acquired Disorders of Plasma Coagulation
- liver disease
- renal disease (nephrotic syndrome)
- vitamin K deficiency
- DIC (disseminated intravascular coagulation)
- Antiphospholipid Antibodies (Lupus Anticoagulant)
- Acquired antibodies to coagulation factors
how does Coumadin (Warfarin) work?
binds to albumin
blocks factor 2, 7, 9, 10
what are some congenital intrinsic Platelet function abnormalities
- Glanzman’s Thrombasthenia
- Bernard Soulier
- Storage Pool Diseases
what is the most common of the congenital intrinsic platelet function abnormalities?
Bernard Soulier
what is another name for Storage Pool Disease?
Gray Platelet Syndrome
comes from platelets not kept moving in storage
thrombophilia
hereditary or acquired disorders that predispose an individual to thrombosis
Congenital Abnormalities under Thrombophilia
- Factor V Leiden Mutation
- Protombin 20210G Mutation
- AT3 Deficiency
- protein C/S Deficiency
what is the most common congenital abnormality and most common acquired abnormality
AT3 deficiency
Out of Protein C/S deficiency, what is the most important?
Protein C
- S supports C
what does Protein S regulate? what does it inactivate and what does it NEED?
regulate so you don’t over clot
- inactivate F5, 8, 10, 2
- NEEDS vitamin K
Risk factors for Thrombosis
- myeloproliferative disorders
- metabolic disorders such as hyperhomocysteinemia
- malignancy
- diabetes
- antiphospholipid antibodies
- microangiopathic disorders such as DIC and TTP/HUS
- Type 2 heparin induced thrombocytopenia (HIT)
Other risk factors that thrombosis can affect
- hormones
- oral conctraceptive
- pregnancy
- vasculitis
- smoking
- stasis (stagnet blood)
- obesity
Lab assessment of thrombosis
- antiphospholipid antibodies
- Quantitation of Inhibitors: AT3, Protein C/S, Tissue Factor Pathway
- Activated Protein C Resistance: Factor V Mutation
- Factor II Mutation
