Hematology - Coagulation Disorders
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- How does Thrombocytopenia present?
-
1) Petechiae
2) Epistaxis
3) CNS bleeds
4) GI bleeds - Bleeding Time is elevated at PL counts less than _____.
- 50,000
- Clinically significant bleeds start at PL counts less than _____.
- 20,000
- CNS bleeds occur with PL counts less than _____.
- 10,000
- What are some causes of Thrombocytopenia?
-
1) Stem cell failure (leukemia, aplastic anemia, alcohol, PNH)
2) Increased platelet destruction
3) Splenic sequestration - What is Idiopathic Thrombocytopenic Purpura (ITP)?
- Autoimmune/autoantibody-mediated PLATELET DESTRUCTION! In kids, follows URI and self-limited. In adults, chronic.
- What are si/sx of Idiopathic Thrombocytopenic Purpura?
-
1) Petechiae
2) Purpura
3) Epistaxis
*normal RBC & WBC morphology - How do you Tx ITP?
-
1st Steroids
2nd Splenectomy
3rd Immunosuppressives (AZT, cyclophosphamide) - What is the classic pentad of Thrombotic Thrombocytopenic Purpura (TTP)?
-
1) Intravascular hemolytic anemia
2) Renal failure (proteinuria, hematuria, inc. creatinine)
3) Thrombocytopenia
4) Neurologic changes
5) Fever - How do you Tx TTP?
- Plasma exchange, or IV immunoglobulin until disease abates.
- Which drugs can induce Thrombocytopenia? (reversible upon stopping drug)
-
1) Heparin
2) Sulfonamides
3) Sulfonylureas
4) Valproic acid
5) Fever Few
6) Abciximab
7) Aspirin - Which bacteria can cause Hemolytic Uremic Syndrome in children?
- E. coli O157:H7
- What are si/sx of HUS?
-
1) Glomerulosclerosis --> ARF
2) Bloody diarrhea, abdominal pain, seizures
3) Fulminant thrombocytopenia with hemolytic anemia - What is Tx for HUS?
- Dialysis
- What do the RBC's look like in TTP?
- Schistocytes (fragmented cells)
- How does Evan's Syndrome cause Platelet destruction?
- IgG autoantibodies --> hemolytic anemia & thrombocytopenia (sometimes pancytopenia)
- What other diseases are associated with Evan's Syndrome?
-
1) TTP
2) Collagen-vascular disease
3) Hashimoto's thyroiditis
4) Leukemia
5) Sarcoidosis - How do lymphomas and leukemias cause platelet destruction?
- Antiplatelet antibodies, induce splenic sequestration.
- How does DIC cause platelet destruction?
- Platelets are trapped in fibrin mesh deposited within vessels.
- What are some causes of splenic sequestration of platelets (leading to thrombocytopenia)?
-
1) Portal HTN
2) Lymphoma
3) Leukemia
4) Massive infection
5) Chronic inflammation -
Autoantibody-Induced Platelet Destruction:
blood smear = _____
Coomb's test = _____
PT/PTT = _____ -
microspherocytes
+
normal -
DIC:
blood smear = _____
Coomb's test = _____
PT/PTT = _____ -
schistocytes
-
elevated -
TTP/HUS:
blood smear = _____
Coomb's test = _____
PT/PTT = _____ -
schistocytes!
-
normal/slightly elevated - What is the most common inherited bleeding disorder?
- von Willebrand Factor deficiency, most commonly Auto Dominant
- vWF is secreted by _____ cells, binds to GP_____, bridging Platelet to _____.
- endothelial cells; GP1b; subendothelial matrix
- How do you Dx vWF deficiency?
-
1) vWF levels
2) Ristocetin-cofactor test (meas. PL aggregation induced by ristocetin binding of vWF) -
vWF:
bleeding time = _____
PT/PTT = _____ -
increased bleeding time
normal PT/PTT - How do you Tx vWF deficiency?
-
1) DDAVP (inc. vWF secretion-only for Type 1)
2) Cryoprecipitate (contains factors VIII, IX, vWF, fibrinogen) - What is Bernard-Soulier syndrome?
-
1) Auto Recessive
2) defect GPIb platelet receptor that binds vWF
3) can't aggregate platelets - How does Bernard-Soulier syndrome present?
- Chronic severe mucosal bleeds & giant platelets on smear
- How do you Tx Bernard-Soulier syndrome?
- platelet transfusion
- What is Glanzmann's Thrombasthenia?
-
1) Auto Recessive
2) defect GPIIb/IIIa receptor platelet receptor that binds fibrinogen - How does Glanzmann Thrombasthenia present, and how do you Tx?
- chronic mucosal bleeds; platelet transfusion
- What is deficient in Hemophilia A?
- X-linked factor VIII deficiency
- How does Hemophilia A present?
- Hemarthroses (bleed into joints) and easy bruising
-
Hemophilia A:
bleeding time = _____
PTT = _____
PT = _____ -
normal
increased
normal - How do you Tx Hemophilia A?
- Recombinant factor VIII, cryoprecipitate
- Can have acquired factor VIII deficiency due to circulating antifactor VIII antibody -- differentiate from genetic by:
- Add patient's serum to control serum. If have antibody, PTT of mixed serum will be prolonged. If genetic deficiency, normal PTT.
- What is missing in Hemophilia B (Christmas Disease)?
- X-linked factor IX deficiency
- How do you Tx Hemophilia B?
- factor IX concentrate
- The _____ makes all clotting factors.
- Liver
- Vitamin K is a necessary cofactor for the enzyme ______ which activates factors: ______ so they can interact with _____.
- gamma-carboxylase; II, VII, IX, X, proteins C & S; calcium.
- Thrombin activates _____, which combines with cofactor _____ to inactivates factors: _____ & _____.
-
Protein C
Protein S
Va & VIIIa -
Liver disease and Vit K deficiency:
PT = _____
PTT = _____ -
much increased
increased - Initial Coumadin administration can cause:
- fulminant skin necrosis secondary to capillary thrombosis (b/c Coumadin also interferes with Protein C synthesis)
- What is the most common inherited HYPERcoagulable disease?
- Factor V Leiden disease, a.a. substitution makes it resistant to cleavage by Protein C --> dysregulated coagulation and high risk DVT and PE
- This congenital hypercoagulable disease is a deficiency in something whose action is enhanced by heparin.
- Antithrombin III, supposed to inhibit Thrombin and factor Xa
- Congenital deficiency in _____ & _____, which cleave factors V and VIII, lead to uninhibited coagulation.
- Protein C & S
- What are some acquired/secondary causes of hypercoagulable states?
-
1) prolonged immobilization
2) pregnancy
3) OCP's
4) smoking
5) diabetes mellitus
6) DIC