Coagulation - Rajan 03.30.15 Flashcards
1
Q
What is Factor V Leiden mutation?
A
- Normal procoagulant activity
- Inactivated slowly by activated Protein C
- INC prothrombinase activity -> failure to remove Va
- Pts also have increased VIIIa/tenase activity -> V a co-factor for VIII inactivation, but V Leiden unable to do this
- Extremely common (5-20% of Caucasian pop)
- Increased risk of venous thromboembolism; 6% of heteros devo VTE by age 65
- Can exist in combo w/other defects
2
Q
What is Prothrombin G20210A?
A
- Mut in 3’ non-coding seq of prothrombin gene
- Mainly N. European mutation
- INC prothrombin syn (>115% of normal) - short PT
- Implicated in both arterial (stroke) and venous thrombosis: <5% heteros devo VTE by 60, and homos devo moderate thrombophilia
- Pregnancy-related thrombosis and complications
3
Q
What is hyperhomocysteinemia?
A
- Acquired (B12, folate) or inherited
- INC homocysteine = higher atherothrombosis; OR INC dramatically when plasma homocysteine >22 umol/L
- Mechs unclear, but also increased venous thrombosis
- Interventional trials haven’t been +
4
Q
What are some causes of acquired thrombophilia?
A
- CHF
- Inflammatory disease
- Nephrotic syndrome
- Diabetes
- MPD, TTP, DIC, HIT, PNH, antiphospholipid syndrome
- Atherosclerosis
- Surgery
- Immobilization, and many more
5
Q
What are some causes of acquired antithrombin deficiency?
A
Pregnancy, liver disease, DIC, nephrotic syndrome, major surgery, acute thrombosis, heparin, estrogen Rx
6
Q
What are some causes of acquired Protein C and S deficiencies?
A
- Protein C: liver disease, DIC, acute thrombosis, Warfarin
- Protein S: pregnancy, liver disease, DIC, inflammation, acute thrombosis, Warfarin, estrogens Rx
7
Q
How is a platelet plug formed?
A
- PLATELETS attach to exposed collagen
- Aggregation of platelets causes release of chemical mediators (ADP, Thromboxane A2)
- ADP attracts more platelets
- Thromboxane A2 (powerful vasoconstrictor): that promotes aggregation & more ADP
8
Q
Is gangrene a sign of bleeding?
A
No
9
Q
A 25 year female is evaluated by you for easy bruisability. She has no h/o epistaxis or menorrhagia. Has a brother who also has easy bruising, no other family with bleeding tendency. She has her wisdom teeth extracted with no bleeding two months ago. On exam you note a high arched palate, and she is double jointed. Her Platelet count, FVIII level, von willebrand ag, von willebrand activity, PT and PTT are normal. Her likely diagnosis is:
A
Likely non-hematologic cause, like collagen disorder
10
Q
What is ristocetin?
A
- Test used to diagnose von Willebrand’s disease -> abnormal agglutination if disease +
11
Q
Pt. comes in with bleeding. What is your plan if platelet count is low? What if it is normal?
A
-
Low:
1. Bone marrow exam
2. Platelet antibodies
3. Screening tests for DIC -
Normal:
1. Bleeding time
2. Platelet aggregation studies with ADP, collagen, adrenaline, and ristocetin
3. O/special platelet tests, e.g., adhesion studies, nucleotide pool measurement
4. vWF, VIII assays
12
Q
What are some causes of thrombocytopenia?
A
- Platelets < 150,000
- Decreased production of platelets: bone marrow failure, chemo, radiation,
- Increased destruction: immune thrombocytopenia, HIT, DIC, post-transfusion purpura, von Willebrand disease, Type 2B, hemophagocytosis
- Increased sequestration: hypersplenism
- Others: Bernard-Soulier, pseudothrombocytopenia (this mean pt has Abs to EDTA, causing aggregating)
13
Q
Know these.
A
Good job!
14
Q
What is immune thrombocytopenia?
A
- Children: acute, treatable; adults: chronic
-
Dx of exclusion: thrombocytopenia not due to DIC, TTP, HUS, artifact, splenic sequestration, primary bone marrow disease (i.e., to distinguish from CLL), etc.
1. No specific or sensitive test for ITP -> can order anti-platelet Abs, but discouraged b/c common
2. Increased MPV; normal PT, PTT - Usually, we do nothing for these ppl if platelet counts >50,000 bc these low numbers idiosyncratically do not prolong bleeding time
15
Q
What is your differential diagnosis? How do you sort this out?
A
- Differential: B12, folate deficiency, hypersplenism alcohol, medications, myelodysplasia, other bone marrow pathology
-
How do you sort this out?
1. Obtain a history and examine the patient
2. Ultrasound of the abdomen (spleen size)
3. Serum B12, RBC folate
4. Bone marrow investigation
16
Q
What are some tests for qualitative platelet abnormalities? KNOW how to interpret this graph.
A
- Bleeding time
- Platelet function analysis
- Platelet aggregation studies
17
Q
What is unique about low platelet count in ITP?
A
- In people w/normal platelet function, bleeding time not prolonged unless platelet count <100,000/mm3
- Ppl w/ITP -> often have normal bleeding times despite very low platelet counts
- Ppl w/qualitative platelet defects, due to aspirin, uremia, or von Willebrand disease, have normal platelet counts, but prolonged bleeding times
18
Q
What are the lab tests for bleeding?
A
- Prothrombin time (PT)/INR
- Partial thromboplastin time (PTT)
- Thrombin time
- Fibrinogen
- Factor assays
- Correction/inhibitors
19
Q
Know this.
A
Good job!
20
Q
Know this.
A
- Good job!
- Note: Factor VIII the only factor that goes UP in the context of liver disease
21
Q
Know this one too. What is the important diagnostic feature of the mixing study?
A
- Lupus anticoagulant: NO CORRECTION ON MIXING STUDY
1. Having thrombocytopenia with this disease not uncommon (bleeding NOT associated with disease -> CLOTTING)
22
Q
Review this.
A
Good job!
23
Q
What are some of the major distinctions between VIII deficiency and vWF deficiency?
A
- VIII: X-linked, normal bleeding time, normal vWF levels, hemarthrosis and hematomas
- vWF: autosomal, prolonged bleeding time, low vWF levels, mucosal bleeding
24
Q
Maybe know this?
A
- Type III: if vWD totally gone, VIII will be totally gone too
25
Know how to read this.
- Of note, in TTP, vWF is longer
- In vWF deficiency, it is shorter, or absent
26
What is Hemophilia A?
- 1 in 10,000 Male Births; X-Linked
- Variable Severity; Hemarthrosis Major Condition
- Just \>5% of Factor VIII- mild disease, 1-5%- Moderate, \<1% Severe
- Therapy with Earlier Cryoprecipitate; **Majority of Adult Hemophiliacs Infected HIV**
- **Mild HA; Desmopressin (DDAVP) → ↑VIII **(stimulates release of vWF from endothelial cells)
- IgG Anti-VIII Inhibitors 10% Patients
1. Activated Factor IX Complex (II,IX,X,VIIa)
2. Exchange Plasmapheresis
3. Increased PTT
27
What is Hemophilia B?
- Xmas Disease; 1 in 100,000 Male Births (X linked)
- **Clinically Identical to Hemophilia A**
- Fresh Frozen Plasma to dilute for hemorrhage
- Antibody Inhibitors less Common
- Increased PTT
- **Treatment**: Factor IX Concentrate (DDAVP not effective)
- Associated with Thrombosis - Activated Impurities
28
What is Hemophilia C?
- Deficiency of Factor XI
- Rosenthal’s Disease
- Autosomal recessive
- Ashkenazi Jews
- PTT prolonged
- Usually mild symptoms
- _Treatment_: FFP
29
What is von Willebrand's Disease?
- Most Common bleeding diathesis -\> 1% prevalence
- Defect platelet adhesion, **↑ Bleeding time**
- VWF stabilizes Factor VIII and protects it from degradation by activated protein C, and also mediates platelet adhesion
- _Symptoms_: **mucocutaneous bleed**, menorrhagia, epistaxis, bruising, surgical risk
- _Treatment_: DDAVP Induces vWF Release, Factor VIII concentrate (high vWF levels)
30
A 22y female with hashimoto thyroiditis, who is currently euthyroid, has been noted with symptomatic cholelithiasis and needs a cholecystectomy. She had wisdom teeth extraction last year with no bleeding. She has no history of epistaxis, menorrhagia or bruising. You perform a CBC, PT and PTT. Her CBC and PT are normal but PTT is prolonged at 45seconds. _A mixing study is not corrected_. What is the next best step:
Lupus anticoagulant testing
31
How does liver disease cause coagulopathy?
- Vitamin K deficiency
- Thrombocytopenia
- Decreased production of clotting factors
- Dysfibrinogenemia
- Increased fibrinolytic activity
32
What coagulation factors are decreased by liver disease, Vit K deficiency, and DIC?
- Liver disease: V, VII, X
- VItamin K deficiency: VII, X
- DIC: V, VII, VIII, X
33
How is Vitamin K involved in coagulation?
- Needed for gamma carboxylation of factors II, VII, IX, X, proteins C & S
- Warfarin inhibits vitamin K carboxylation, induces deficiency state for over a week.
- Rapid ↓Factor VII, initially ↑PT, later ↑PTT.
- Deficiency results from nutritional deficits, antibiotic use, fat malabsorption
34
What are the characteristics of Vitamin K deficiency?
- Mild PT prolongation: asymptomatic
1. Vitamin K, PO or SC; avoid IM, careful IV
- Anticoagulant dependent patients
1. Titrate correction; response 6 - 12 (48) hours
- Severe ↑PT or Symptomatic -\> FFP
- Liver disease: ↓Factor synthesis, K Stores
1. Vit K often ineffective -\> FFP, cryoprecipitate if low fibrinogen
