Hemostasis Defects Flashcards
What factors does protime (PT) measure?
II, VII, X, V and fibrinogen
The extrinsic and lower part of the coagulation cascade.
What is a normal PT?
9-12 seconds
Because the PT is dependent upon the potency of the material that i used to start the reaction in the laboratory what must it be compare to?
International normalized ration (INR)
What is a normal INR?
1.0
What are two of the most common causes of abnormal PT?
Deficiency of vitamin K dependent factors (VII, X, II) or
Inadequate liver funciton
What would warfarin do to the PT?
Increase PT
What does the PTT measure?
The procoagulant activity of the entire pathway, but it is more sensitive to deficiencies of the higher numbered factors especially XI, VIII, and IX
What is PTT not effective in measuring?
Factor VII
What can prolong the PTT?
Heparin or acquired anticoagulants such as fibrin split products
Patients with hemophilia
What is a normal PTT?
25-32 seconds
What is PT used to monitor?
What is PTT used to monitor?
- Warfarin
- Heparin
What does thrombin time measure?
The procoagulant activity of fibrinogen and is also very sensitive to the anticoagulant effect of heparin or fibin split products.
What is the normal range of thrombin time?
12-18 seconds
What does the bleeding time measure?
Platelet and vessel initeraction as well as the number and the function of platelets.
What is a normal bleeding time?
2-9 minutes
What will cause an increase in bleeding time?
Severe decrease in platelet count
von Willebrand disease
abnormalit in platelet function
OTHER FACTOR DEFICIENCIES DO NOT PROLONG THE BLEEDING TIME
What is PFA-100?
Platelet function analyzer that can perform an in vitro bleeding time
What is most common cause of a severe bleeding tendency?
Hemophilia A (Factor VIII deficiency)
Hemophilia B is characterized as a deficiency of what coagulation factor?
Factor iX
What is the inheritance pattern of both Hemophilia A and Hemophilia B?
X-Linked
Females are carriers
Men are affected
Which test is prolonged in Hemophilia A and B?
PTT
What is the genetic defect is seen in 40% of Hemophilia A patients?
Inversion on the long arm of the X chromosome
Less than 1% factor activity is considered a severe hemophilia. What are the symptoms of someone with less than 1% factor activity?
Spontaneous hemorrhaging into their joints, muscles, soft tissues, retroperitoneal space and CNS.
Continuous bleeding into the joints leads to very severe arthritis
Between 2%-5% factor activity is considered to by a moderate hemophilia. What are the symptoms of someone with moderate hemophilia?
It usually takes some degree of trauma to cause bleeding in these patients
> 10% factor activity is considered a mild hemophilia. What are the symptoms of someone with >10% factor activity?
Only bleed after trauma and do not develop the chronic joint disease
They are usually diagnosed after a bad traumatic even ot after a bad result from surgery
Female carriers can express anywhere from 30-100% factor activity, but at what percent are they symptomatic carriers?
30%
Factor XI deficiency usually express >5% factor activity. Are they spontaneous bleeders?
No usually
What is the inheritance pattern of Factor XI deficiency?
Autosomal recessive
What patient population is Factor XI deficiency common in?
Ashkenazi Jews
What test time is usually prolonged in Factor XI deficiency?
PTT
When is Factor XI deficiency most commonly diagnosed?
Post-operative hemorrhage
What test time is usually prolonged in Factor VII deficiency?
JUST PROTIME
What is the inheritance pattern of Factor VII deficiency?
Autosomal disease: Homozygous severe but heterozygous still affected.
What are the two functions of von Willebrand protein?
- Adhere platelets to exposed collagen at the wound site.
2. Carrier of Factor VIII
What two tests are prolonged in von Willebrand’s Disease?
PTT
Bleeding time
What is type I von Willebrand’s disease?
Deficiency of normal von Willebrand protein
What is type II von WIllebrand’s disease?
Presence of an abnormal protein
DDAVP (arginine vasoprressin is very effective in treating which type of von Willebrand’s disease?
Type I
What is the inheritance pattern of von Willebrand’s disease?
Autosomal dominant
What are some symptoms of von Willebrand’s disease?
Bleeding from mucosal mebranes, and nose bleeds, GI bleeds and menorrhagia
They also bleed after surgery
Acquired Factor VIII inhibitor is an extremely rare acquired factor inhibitors seen in postpartum or advanced age patients.
How does this acquired disease present?
What test is prolonged?
- Soft tissue and muscle bleeding, and usually marked hematomas of their skin or mucosal bleeding
- Abnormal PTT only. Which will not correct after two hours of incubation.
What is the prognosis for Aquired Factor VIII inhibitor?
Although the disease has a 25% mortality due to bleeding it has an EXCELLENT long-term prognosis since most patients respond to immune suppression.
Name some very rare acquired inhibitors that can be seen.
Inhibitors to von Willebrand protein
Factor II inhibitors
Factor V inhibitors
Where are most coagulation factors synthesized?
Liver
What are the factors that are especially lowered due to liver disease?
Factor V Factor II Factor VII Factor IX Factor X Fibrinogen
What tests are prolonged in liver disease?
PT
Relatively less prolonged PT
Thrombin time may also be prolonged
In liver disease you should always make sure that there is not a component of ____________ deficiency
Vitamin K
Vitamin K is obtained from the diet. What two circumstance cause vitamin deficiency?
No oral intake and broad spectrum antibiotics
A 16 year old patient is brought into the emergency room by his parents. He is unconscious and his parents report that he suffers from depression and that they found a box of d-Con by his bed. They show you the box that has an upside-down rat on it. Based on your knowledge of rat poison you know that this patient will need what type of therapy? Besides charcoal and gastric lavage blah blah blah
Vitamin K therapy for many months
What two tests are decreased in disseminated intravascular coagulation?
Fibrinogen level is decreased
Platelet count is low
Fibrin cleavage products, fibrin degradation products and D-dimer can be measured in DIC. These products can inhibit two tests. Which two tests?
PTT»_space;>it being prolonged
TT»».it being prolonged.
What two factors are consumed in DIC?
Factor VIII and Factor V
How is DIC distinguished from liver disease just based on the labs?
Liver disease PT is prolonged a lot more than PTT
DIC: PTT is increased relatively much more than the protime
Define thrombosis
Formation and propagation of clot within the vasculature
Thrombosis occurs due to some combination of what three factors?
Stasis
Inflammation
Vessel wall injury
What factors create a hypercoagulable state?
Chronic damage to vessel walls
Excess of procoagulant factors
Deficiency of anticoagulant facotrs
Fibrinolytic activity
Name four risk factors for thrombosis
- A thrombotic episode in the absence of a defined precipitating condition
- Recurrent episodes of throbosis, or throbosis at an early age and is otherwise health
- A severe, life threatening thrombosis, or thrombosis at an unusual site
- Family history of thrombosis
Is it appropriate to search for an underlying hemostatic defect that can contribute to a “hypercoagulable state”?
Yeah
Lupus anticoagulant is
rare or common?
congenital or acquired?
Common acquired abnormality
What is the pathogenicity of Lupus anticoagulant?
IgG antibody which reacts against phospholipid in the platelet membrane or endothelial cell
What test is prolonged in lupus anticoagulant?
Prolongs the PTT
What are some symptoms of lupus anticoagulant?
Deep vein throbosis, pulmonary embolism, thrombotic strokes and recurrent miscarriage due to thrombotic disease of the placental blood
Is PTT corrected when normal plasma is mixed with the plasma from a patient with lupus anticoagulant?
no
What are the most common familial congenital condition which cause hypercoagulable syndromes?
Deficiencies of
- antithrombin (AD)
- protein C (AD)
- protein S (AD)
- resistance to protein C (Factor V Leiden)
What are the symptoms of someone who has homozygous deficiencies in either protein C or S?
Heterozygous
Fetal at birth
Presents after puberty with recurrent venous thrombotic disease
Mutation in Factor V causes it not to inactivated by ________.
Which patient population are heterozygous states common?
Protein C
Europeans
