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64 Cards in this Set

  • Front
  • Back
What are promoters of the coagulation cascade?
Tissue factor (extrinsic)
Intrinsic pathway
Fibrinogen, Factor XIII,Fibrinolysis
Which clotting factor is unique to PT?
Factor VII
Factor VII
What factors are unique to PTT?
In the context of bleeding:
XI
IX
VIII

Other:
XII
In the context of bleeding:
XI
IX
VIII

Other:
XII
What factors are in the overlap between PT and PTT?
Thrombin
X
V
Thrombin
X
V
What are the inhibitors of tissue factor?
Tissue factor inhibitor
What are the inhibitors for the intrinsic pathway?
Protein S
Protein C
What is the activity of Protein S, C?
Cleaving factor V, VIII
What is antithrombin?
Degrades thrombin
Degrades X
What is the activator of antithrombin?
Endogenous Hepaprans
What are endogenous heparans? What do they activate?
Proteins that inhibit clotting

Antithrombin
What are the two forms of protein S? How do they work? What implications does this have
Bound: bound to C4b
Free: able to complex with C

In serious infections, C4b BP is upregulated. As a result, you get less activation of the protein C/S, which leads to less degradation of V and VIII. As a result, people with infections are prone to clot.
What happens when fibrinogen is cleaved?
1. Loses solubility
2. Monomers come together
3. Formation of large thrombin complex
What is the activity of factor 13?
Cross linking of thrombin chains
What is the site of TPA release?
Endothelium around the site of damage
What is the activation of TPA?
Activates tissue plasminogen, which cleaves the fibrin
Where is tissue plasminogen released?
From the liver
What are causes of increased PT and aPTT?
Medical conditions:
-Anticoagulation
-DIC
-Vitamin K deficiency
-Liver disease
-Massive tranfusion

Dysfibrinogenemias

Acquired inhibitors to factors V, II, and X
What processes are dysregulated in DIC?
Thrombin acting: procoagulation

Plasmin acting: fibrinolysis
What is the presentation of someone with DIC?
Accute hemorrhagic disorder

Indolent, subacute thrombotic disorder (presenting with bleeding)
What are serious consequences of DIC?
-Multiorgan failure due to multiple ischemic events
-Thrombocytopenia`
What are causes of acute DIC?
INFECTION
Obstetric
Malignancy
Trauma
Other
What are some infectious causes of DIC?
Gram negative sepsis
Viremia
Parasites
What are some obstetric causes of DIC?
Abruption (placenta separates from endometrial wall)
Amniotic fluid embolism (fluid gets into body)
Eclampsia (HTN in pregnancy)
What are some malignant causes of DIC?
Acute promyeocytic leukemia
What are some traumatic causes of DIC?
Crush injury
Freshwater drowning
Heat stroke
Snakebites
What are some other causes of DIC?
Homozygous protein C and S deficiency
Severe liver disease
HIT (heparin induced thrombocytopenia)
What are some broad causes of subacute DIC?
Malignancy
Obstetric
Vascular
What are some malignant causes of subacute DIC?
Mucinous adenocarcinoma/Trousseau syndrome
What are some obstetric causes of subacute DIC?
Retained dead fetus
What are some vascular causes of subacute DIC?
Hemangioendothelioma
Venous thromboembolic disease
Chronic renal failure
How do you go about diagnosing DIC?
Screening:
aPTT: prolonged
PT: prolonged
Fibrinogen: decreased
Platelet count: decreased

Confirmatory:
D-dimer: elevated
Fibrin degradation products: elevated
What is your "cash money" test for DIC?
D-dimer
What conditions should you order up a D-dimer for?
DIC
DVT
PE (high NPV, low PPV)
What's the treatment for DIC?
Get the underlying condition!!!
Replace different components
Heparin
What's the therapy for APML? How does this work?
All trans retinoic acid

It induces the cells to differentiate to a further stage, causing them to not cause DIC
IN what DIC scenarios should you use heparin?
Acute cyanosis
Digital ischemia
Purpura fulminans
Retained dead fetus
Migratory thrombophlebitis
What does a smear of microangiopathic hemolytic anemia look like?
Shistocytes (RBC fragmentations)
Small RBCs (microcytes)

NO PLATELETS!
Shistocytes (RBC fragmentations)
Small RBCs (microcytes)

NO PLATELETS!
What type of hemolysis happens in the microangiopathic hemolytic anemias?
Intravascular hemolysis
Where are the red cells disposed of in the microangiopathic hemolytic anemias?
The spleen/reticuloendothelial system
What are some potential causes of microangiopathic hemolytic anemias?
DIC
Thrombotic thrombocytopenic purpura
Hemolytic uremic syndrome
Malignant hypertension
Aortic stenosis
HELLP syndrome
Heparin-induced thrombocytopenia
Severe glomerulonephritis
What are the classic symptoms of thrombotic thrombocytopenic purpura?
Microangiopathic hemolytic anemia
Thrombocytopenia
Renal involvement
Neurologic signs
Fever
What is the cause of thrombotic thrombocytopenic purpura?
Acquired autoantibodies that inhibit ADAMTS13

You can get giant vWF complexes
What is the function of ADAMTS13?
Metalloprotease that cleaves vWF
What is the name for congenital thrombotic thrombocytopenic purpura?
Upshaw-Schulman syndrome

DEFICIENCY of ADAMTS13
What's the treatment for thrombotic thrombocytopenic purpura?
Plasma exchange

Immunosuppression
What are the findings in DIC vs. TTP?
What are the procoagulents that have a vitamin K tacked on?
II
VII
IX
X
What are the anticoagulents that have a vitamin K tacked on?
Protein C/S
What reaction is assisted by vitamin K?
Gamma carboxylation: glutamic acid-->gamma carboxyglutamidc acid
What enzymes regenerate vitamin K?
Quinone reductase
Epoxide reductase
What enzyme is the target of warfarin?
Epoxide reductase
What are some causes of vitamin K resorption deficiency?
Nutritional deplertion
Antibiotic
Warfarin
What labs are off if there is liver disease?
Factor VIII elevated

Factor V decreased

Late in the game, fibrinogen falls
What parts of the coagulation cascade are synthesized by the lungs?
Factor VIII
vWF
How do you differentiate between liver disease and vitamin K deficiency?
Factor V

IN liver disease, it, along with the other clotting factors from the liver are low

IN K deficiency, levels of V stay high, as it's not dependent on vitamin K
What is the definition of a massive transfusion?
Adults: 4 units RBC in < 4 hrs, ongoing uncontrolled bleeding
Child: 1/2 blood volume in <4 hours and ongoing, uncontrolled bleeding
What are the complications secondary to a massive transfusion?
Coagulopathy:
-Drops in levels of clotting factors
-Citrate binds calcium-->lack of clotting
What are some of the super rare acquired coagulation protein defects?
Dysfibrinogenemia
Inhibitors to X, V, II and fibrinogen
Hypergammaglobulinemia
Systemic amyloidosis
Heparinoids
Factitious
What are some causes of hypergammaglobulinemia?
Multiple myeloma (IgG)
Waldenstrom macroglobulinemia (IgM)
What are the findings in systemic amyloidosis related to clotting?
Decreased factor X/IX
What are heparinoids?
Heparin-like anticoagulents produced in patients with an underlying malignancy
What acquired disorder is associated with ONLY a prolonged aPTT?
Inhibitors to factor VIII
What are the symptoms of someone having inhibitors to factor VIII?
Prolonged aPTT, normal PT
Skin ecchymoses, tissue hematomas
What's the treatment for having inhibitors to factor VIII?
IMmunosuppression
Treat the bleeding