Hemostasis and Thrombosis Flashcards
What are the sequential steps that arrest bleeding?
- vascular reaction - vasoconstriction
- formation of platelet plug (primary hemo)
- activation of the coagulation cascase (stable fibrin clot - secondary hemo)
Describe what happens during primary hemostasis?
- collagen and von Willebrand factor is exposed due to injury to endothelial cell wall
- platelets roll over that and stick
What are the factors of the extrinsic pathway?
7–>X–>5–>2 (Prothrombin)–>2a (Thrombin) –>1 (Fibrinogen)–>Fibrin–>13 (Tight clot)
NB: X marks the spot for the common pathway
NB2: 13 is not measured in PTT or PT
What are the vitamin K dependent factors?
10, 9, 7, 2 (1972 - it was a good year!)
NB: Vitamin K is more associated with the extrinsic pathway, but really, there are factors on both sides of the pathway. Mortier told me it is more important for 7 than 9.
What happens if you are deficient in Protein C or Protein S?
You clot out of control (predisposed to major thrombosis)
What are the factors of the intrinsic pathway?
TENET - Twelve, Eleven, Nine, Eight, Ten (common)
Then remainder of common pathway - 5, 2, 2a, 1, Fibrin, 13
aPTT/PTT measures coagulation in which pathway?
Instrinsic (PITT)
PT measures coagulation in which pathway?
Extrinsic (PET)
What are the important PMH and FH questions to ask a patient regarding bleeding?
- Bleeding Hx - bruises, petechhaie, gingival bleeding, etc.
- deep muscle and joint bleeding
- hematemesis, melena, hematuria, hemotypsis
- liver or kidney disease
- aspirin, NSAIDs, Plavix, warfarin, heparin use?
- menstrual bleeding hx
- bleeding during or after surgery that was hard to control
- blood relative with bleeding disorder
- anemia
What are the common pitfalls of laboratory studies?
- heparin in sample
- traumatic venipuncture (slow draw)
- too little sample in tube
- polycythemia (too much anticoag in vaccutainer)
- anemia (too little anticoag)
- specimen sits at room temperature
- PFA shaken and stirred (too much disruption)
What is PT used for?
- extrinsic and common factors
- used to monitor Coumadin patients
What happens to PT with a Vitamin K deficiency?
It is prolonged
When is PTT prolonged?
- von Willebrand disease
- hemophilia
- lupus anticoagulant
- NB: sensitive to Heparin contamination
What does a 1:1 mixing study tell you?
- if it corrects into the normal range, a factor deficiency is the likely culprit
- if it fails to correct, an inhibitor or anticoagulant is the likely suspect
- NB: 30% activity is the threshold to correct clotting times
What is the Platelet Function Assay (PFA-100)?
- modern test that replaces old “bleeding time” test
- push blood through a coated filter and watch the clot formation time on the filter
- need platelets at least 100 x 109/L
When will the Platelet Function Assay be prolonged?
- von Willebrand disease
- aspirin
- platelet function defects
What does a Normal PT/PTT indciate in the presence of a bleeding disorder?
Factor XIII deficiency
Remember, it is not measured by PT/PTT
What does both an abornmal PT and PTT suggest?
- fibrinogen deficiency/problem
- Vitamin K deficiency
- DIC
- Liver disease (PT abnormal first)
What does an abnormal PTT with normal mixing result suggest?
- Hemophilia A or B
- Von Willebrand disease
- Factor XI deficiency
- Factor XII deficiency
What might cause a fibrinogen deficiency?
- liver dysfunction
- DIC
Can a reduced level of fibrinogen cause a prolonged PT, PTT or Thrombin Clot Time?
- Generally, no unless fibrinogen is less than 100 mg/dL
What does Thrombin Clot Time (TT) measure?
Measures the time for conversion of fibriongoen to fibrin
Heparin can contaminate
What is von Willebrand disease?
- Caused by a deficiency or reduced functioning of von Willebrand factor
- carries and stabilizes factor VIII
- mediates platelet adhesion and aggregation
What is the most common inherited bleeding disorder?
von Willebrand disease
What is the mechanism of inheritance of von Willebrand disease?
Usually autosomal dominant
What kind of bleeding do you see in von Willebrand disease?
platelet bleeding or primary hemostasis bleeding
What is the Rx for von Willebrand’s disease?
- DDAVP (Arginine vasopression) - releases stored vWf from endothelial cells
- reduced efficacy with repeated dosing (tachyphylaxis)
- Humate-P - factor VIII product that contains vWf
- Cryoprecipitate - life-threatening bleeds (infectious transmission risks)
- Aminocaproic acid - Amicar - supportive, effective for mucosal bleeding. acts by stabilizing clot. No for hematuria
What is Hemophilia A?
Deficiency or lack of Factor VIII
What is Hemophilia B?
Lack or deficiency of Factor IX
How are Hemophilia A and B transmitted?
- X-linked recessive disorders
Hemophilia - Epidemiology
- Factor VIII (80%)
- Factor IX (15%)
- Expressed in males, carried in females (some females can have prolonged bleeding in surgery or trauma)
- approx. 30% new mutations
What are the three degrees of severity of hemophilia?
- Mild Hemophilia (30-40% of cases)- Factor level 6-50%/uncommon spontaneous bleeding/see sx after major trauma or surgery
- Moderate hemophilia (10% cases) - factor level 1-5%/see sx after minor trauma/4-6 bleeding episodes per year
- severe hemophilia (50-70%) - Factor level <1%/spontaneous bleeding occurs/2-4 x month
What are some of the history questions to ask about hemophilia?
- family history
- bleeding with circumcision
- prolonged bleeding with heel stick or vaccination
- easy bruising
- intracranial hemorrhage (esp. during childbirth)
- milder phenotypes may not present until later ages
What type of bleeding episode is most common in hemophila?
joint bleeding (60%)
most common sites are knee, ankle, elbow
What should you avoid when treating a joint bleed?
NSAIDS and Aspirin (you know why)
Where are common sites for muscle bleeds in hemophilia?
- gluteus
- hamstrings
- iliopsoas
- calf
- quadriceps
- deltoid
- biceps
What are the possible complications of untreated muscle bleeds?
- foot drop
- flexed hip
- volkmann’s contracture (hand arm)
- compartment syndrome
What are the key points of assessment for a joint/muscle bleed?
- pain - tingling or burning
- disuse or immobility
- abnormal appearance - circumference
- tenderness and heat
- nerve involvement
What is the treatment for Hemophilia?
- replacement of missing factor concentrate (on demand/prophylaxis)
- DDAVP/ Stimate
- Antifibrionolytic agents - Amicar
- Supportive measures - RICE and pain control
What are factor inhibitors and how do you identify when they exist?
- these are antibodies that develop against “foreign” infused factors in hemophilias. They exist in 15-25% of Factor VIII pts and 1.5-3% of Factor IX pts.
- median of 9-12 exposure days
- consider when pt. is unresponsive to Rx
- prolonged PTT after mixing 1:1
- one BU of activity causes 50% loss of Factor VIII activity
How do you treat inhibitors in hemophilia?
- recombinant FVIIa - push clotting through extrinsic pathway
- High-dose VIII or IX
- prothrombin complex concentrates
- can try to desensitize the immune system to the factor
What do you do first when a pt. with hemophilia presents with major bleed symptoms?
- TREAT FIRST
What is DIC?
- A disorder of secondary hemostasis caused by consumption of factors in the coagulation system
- triggered by exposure of blood to tissue factor
- present with bleeding, petechiae and purpura
- causes include: infection; major trauma; malignancy
What is the Rx for DIC?
- Most important: TREAT UNDERLYING CAUSE
- hydration
- RBC transfusion
- if bleeding, fresh frozen plasma, cryoprecipitate, or platelets
What are conditions that can lead to thrombosis?
Virchow’s Triad
- alterations in blood flow (stasis)
- vascular endothelial injury
- alterations in constituents of blood
50% of thrombotic events in pts with inherited thrombophilia are affiliated with additional risk factor
What are the causes of inheritied thrombophilia?
- Factor V (Leiden) - most common inherited in causasians 3-8%
- prothrombin gene mutation (G20210A)
- Protein S deficiency
- Protein C deficiency
- antithrombin deficiency
What is the Rx for venous thromboembolism?
- LMW heparin, vondaparinaux, unfractioned IV heparin
- overlap with and transition to Vitamin K antagonist
- Target INR 2.5
Who should be screened for thrombophilia?
- initial thrombus occuring before 40 without provoking factor
- FH of 1st degree relatives with VTE
- recurrent VTE
- thrombosis in unusual vascular beds - liver, cerebral, mesenteric
What are secondary hypercoagulable states?
- pregnancy
- contraceptive use/HT
- malignancy
- systemic inflammation
- post-operative state
- immobilization
- trauma
von Willebrand Disease Panel has what tests?
- vWF:RCo (Ristocetin) - decreased in vW
- vWF:Ag (Antigen) - decreased (but can be normal with non-functional vW)
- FVIII (can be normal)
