Bleeding/Clotting disorders - H/O Flashcards
1
Q
Primary Hemostatic Defect
A
- Problem with platelets (or vascular wall)
- Congenital: relatively common
- Acquired: very common (drugs)
- Clotting labs normal
- Prolonging initial bleeding
- CBC (platelet count)
- Platelet function testing
- Von Willebrand panel
2
Q
Secondary Hemostatic Defect
A
- Problem with clotting factor(s)
- Congenital: uncommon
- Acquired: very rare if so think autoimmune
- late re-bleeding
- PT / INR, aPTT, fibrinogen
- Mixing studies
- Factor levels
3
Q
Prothrombin time /INR - what prolongs it
A
- coumadin
- liver disease
- Vitamin K deficiency (II, VII, X)
- Genetic Factor deficiency (II, V, VII, X)
- DIC
- Not enough fibrinogen
- dysfunctional fibrinogen
4
Q
Partial Thromboplastin Time (PTT) - what prolongs it?
A
- Heparin
- Factor VIII deficiency (hemophilia A)
- Factor IX deficiency (Hemophilia B)
- Factor XII deficiency
- Factor XI deficiency
- Other factor deficiency (II, V, X)
- Not enough fibrinogen
- dysfunctional fibrinogen
- antiphospholipid antibodies
5
Q
von Willebrand Disease
A
-Most common inherited bleeding disorder
-Prevalence in general population is ~ 1%
-Many asymptomatic individuals
-Caused by mutations in the gene coding for von Willebrand factor, resulting in quantitative and/or qualitative deficiency
-Functions of von Willebrand factor:
Platelet adhesion to endothelial injury
Plasma carrier of factor VIII
-Autosomal dominant inheritance, males and females affected
6
Q
von Willebrand Disease: Classification
A
Type I -Most common (70%) -Partial quantitative deficiency -May be very mild Type II -Qualitative abnormalities of vWF - doesnt work as well -Several subtypes Type III -Virtually complete deficiency of vWF -Rare (~1 in 1 million) -Autosomal recessive inheritance pattern
7
Q
von Willebrand Disease: Symptoms
A
- Clinical presentation depends on severity
- Epistaxis, dental bleeding, bruising, menorrhagia
- Prolonged bleeding from wounds (primary hemostasis)
- Severely affected individuals may have joint and soft tissue hemorrhages
8
Q
von Willebrand Disease: Diagnosis
A
- Normal INR
- Normal or mildly prolonged aPTT
- Normal platelet count
- Abnormal PFA-100 (PFCT)
- Low von Willebrand antigen
- Low factor VIII
- Low ristocetin cofactor activity
9
Q
von Willebrand Disease: Treatment
A
- Avoid drugs that inhibit platelet function - ASA, Ibuprofen
- DDAVP (desmopressin)/Stimate
- Synthetic analogue of anti-diuretic hormone (vasopressin)-use high concentration
- Releases stored vWF from endothelium
- Given intravenously or inhaled-not orally!
- Cant use every day - Amicar or Lysteda - oral antifibrinolytics - stops clot from breaking down, doesnt make blood clot form
- Plasma derived factor VIII concentrate (Humate-P, Wilate, Alphanate) - if severe VWD
- Cryoprecipitate
10
Q
Hemophilia
A
- Congenital bleeding disorder caused by deficiency of coagulation factor VIII or IX
- Genes for factors VIII and IX located on the X chromosome
- Females are carriers, males are affected
- High rate of spontaneous mutations: 30% of patients have no family history of hemophilia
11
Q
Hemophilia A
A
- Factor VIII deficiency
- Classical hemophilia
- 1 in 5,000 to 10,000 male births
- Hemophilia affects all racial and socioeconomic groups equally
- There are 20,000 hemophiliacs in the United States
- 400,000 hemophiliacs worldwide
12
Q
Hemophilia B
A
- Factor IX deficiency
- Christmas disease
- 1 in 30,000 male births
13
Q
Hemophilia: Diagnosis
A
- Normal INR
- Markedly prolonged PTT
- Normal platelet count and function
- Measure specific factor levels
14
Q
Clinical Features of Hemophilia
A
- Severity of bleeding tendency depends on the factor level
- Joint bleed (hemarthrosis)
- Soft tissue bleeding
- Deep muscle bleeds
- Intracranial bleeds
Mild ( > 5% )
- Bleed only after severe injury, trauma, or surgery
- May not be diagnosed until adulthood
Moderate (1-5%)
- Bleed after injury, surgery
- May have occasional spontaneous bleeding
Severe ( < 1 %)
- Frequent spontaneous bleeding
- Diagnosis made in early childhood
15
Q
Hemophilia: Treatment
A
- Proper treatment requires direct involvement of specialists experienced in the management of bleeding disorders
- Avoid drugs that impair platelet function
- Factor VIII or IX concentrates: Plasma derived (not done anymore), Recombinant
- On demand vs. prophylactic factor replacement
- VERY expensive
- Most of the world’s hemophiliacs do not have access to factor concentrates
16
Q
Neonatal Vitamin K Deficiency
A
- In US Vit K is given prophylatically (1mg IM) on day 1 of life.
- Based on large studies that demonstrated the benefits using clinical bleeding as outcome
- Neonates are high risk due to low placental transfer and limited liver storage
- Some risk groups require additional prophylaxis
- Alpha-1 antitrypsin def , chronic diarrhea, CF and celiac dz.
- Mothers on anticonvulsant therapy during pregnancy
17
Q
Adult Vitamin K Deficiency
A
CAUSES
- Chronic or severe illness
- Malnutrition-chronic TPA, alcoholism, IBD
- Parenchymal liver disease
- Cystic fibrosis
- Drugs - Antibiotics (cephalosporin), cholestyramines, warfarin, salicylates, anticonvulsants, and certain sulfa drugs are some of the common causes of VK deficiency
TREATMENT
- VK-1 should be administered subcutaneously or intramuscularly.
- If there is a high risk for hematoma formation with intramuscular or subcutaneous VK administration, then an oral form of VK can be administered
- The absorption with the oral form is variable because it requires bile salts in the ileum for absorption. This form is used in the setting of asymptomatic VK deficiency.
18
Q
What happens when we have too much hemostasis ?
A
- Arterial Thrombosis: stroke, heart attack
- Venous Thromboembolism: DVT, PE
19
Q
Genetic Thrombophilia
A
Factor V Leiden and Prothrombin Gene Mutation
- Autosomal dominant inheritance
- Single point mutations
- Well-known, and VERY common
- Many asymptomatic carriers
Protein C deficiency and Protein S deficiency or Antithrombin-III deficiency
- Autosomal dominant inheritance
- Many different mutations described
- Well-known, but uncommon
- Usually have strong family history of thrombosis
- Dysfibrinogenemia
- Elevated levels of factors VIII, IX, XI, and fibrinogen are also probably inherited hypercoagulable state
20
Q
Mechanisms of Thrombosis in Inherited Thrombophilia
A
- Failure to control thrombin generation
- Factor V Leiden heterozygote = 5 – 7 fold increased risk
- Prothrombin Gene Mutation
- Protein C deficiency
- Protein S deficiency - Impaired neutralization of thrombin
- Antithrombin-III deficiency
21
Q
Acquired Thrombophilic Conditions
A
- Antiphospholipid antibodies
- Malignancy
- Inflammatory Bowel Disease
- Nephrotic syndrome
- Myeloproliferative Disorders
- PNH
- CHF
- Sepsis / DIC
- HIT
22
Q
Acquired Triggers for Thrombosis
A
- Immobilization
- Surgery
- Trauma
- Pregnancy / Postpartum
- Estrogens (OCPs, HRT) = 3 – 4 fold increased risk
- Older Age
23
Q
Diagnosis of VTE
A
- Clinical signs and symptoms
- Lab testing: D-dimer
- Breakdown of cross-linked fibrin clots releases D-dimers
- D-dimer levels can be measured by laboratory tests
- Elevated levels may also be seen with: cancer, infection, trauma, surgery, pregnancy, inflammation
- Elevated levels may persist for 3+ weeks - Non-Invasive Imaging
- Compression ultrasound: Unable to compresses vein = DVT
- V/Q scan
- CT scan
- Invasive Imaging
- Venography
- Pulmonary angiography
24
Q
DVT: Clinical Findings
A
- Pain
- Swelling
- Tenderness
- Discoloration
- Warmth
- Asymmetry
25
Q
PE: Clinical Findings
A
- Dyspnea
- Chest Pain
- Anxiety
- Cough
- Hemoptysis
- Sudden Death
26
Q
Treatment of Venous Clots
A
-Heparin-unfractionated
-Low MW Heparin
enoxaparin (Lovenox)
dalteparin (Fragmin)
-Factor Xa Inhibitor
fondaparinux (Arixtra)
-Direct thrombin inhibitors
lepirudin
argatroban
bivalirudin
Long term: Warfarin, coumadin, jantoven
27
Q
Treatment of Venous Clots
A
- The best way to treat a clot is to prevent it from forming in the first place
- Anti-platelet medications offer NO PROTECTION against venous thrombosis
- Anti-platelet drugs, warfarin, and heparins DO NOT dissolve clots directly
- Treatment decisions MUST include an assessment of the risks: recurrent clot vs. bleeding
- All long term treatment decisions should be re-evaluated periodically to be sure the benefits still outweigh the risks
- New drugs are different, not necessarily better
