Coagulation Disorders Flashcards
1
Q
platelets
A
- Not as simple as you thought.
- Platelets are actively inhibited by the endothelial lining of blood vessels (via NO and ADPase)
- Endothelial injury exposes collagen and releases von Willebrand’s Factor (vWF), which activates platelets.
- When activated, platelets change shape.
- Platelets aggregate, using fibrinogen and vWF (among many other proteins)
- They also adhere to exposed collagen, using GPIa, actin, and myosin
2
Q
after the clot
A
- Blood is constantly wavering between clotting and dissolving of clot (thombolysis).
- Protein C (activated by Protein S) and antithrombin work to inactivate clotting factors.
- TFPI (tissue factor pathway inhibitor) also works in inactivating Xa and thrombin.
- But, most important, is the plasminogen-plasmin factor pathway…..
3
Q
bleeding disorders
A
- Defined as excessive or repetitive bleeding, or bleeding at unusual sites.
- Bleeding from problems with platelets usually involves skin and mucosa (epistaxis, gum bleeding, menorrhagia).
- Bleeding from clotting factor deficiencies usually involves the skin and muscles. Can be severe (hemathroses) in some cases.
- May be congenital or acquired.
- Congenital (usually a single defect) (vascular integrity, platelet function, fibrinolysis, coagulation factors)
- Acquired (involves multiple systems: liver, kidneys, collagen, immune) (cancer, infection, shock, obstetrics, malabsorption, AI disorders, drugs (NSAIDs, aspirin, thiazides, anticoagulants))
4
Q
laboratory studies
A
- Platelet count, peripheral smear, bleeding time.
- Prothrombin time (PT), partial thromboblastin time (PTT), activated PTT, or INR.
- Thrombin clotting time (measures rate of conversion between fibrinogen and fibrin).
- Some problems may require more specialized studies.
5
Q
thrombocytopenia
A
- The most common cause of abnormal bleeding.
- Abnormal decrease in the number of platelets.
- Causes: impaired production, increased destruction, splenic sequestration, dilution.
- Usual presentation is petechiae and/or purpura on the skin and mucous membranes.
6
Q
ITP: idiopathic thrombocytopenic purpura
A
- Acute: most commonly in children, self-limited, autoimmune, associated with a recent viral URI.
- Chronic: any age (20-50 most commonly), more common in women, often associated with other autoimmune disorders.
- Acute: abrupt appearance of petechiae, purpura, or even hemorrhagic bullae on skin and mucous membranes.
- Chronic: usually milder (petechiae only).
- Patients are otherwise well appearing; may also complain of epistaxis, menorrhagia, or oral bleeding.
7
Q
lab findings in ITP
A
- Decreased platelets (Acute: 10,ooo—20,ooo/μL, Chronic: 25,000—75,000/μL)
- Possible mild anemia
- Peripheral smear shows megathrombocytes
- Coags (PT, PTT, INR) are normal
8
Q
treatment of ITP
A
- Acute: usually self-limited, resolves spontaneously. (May require steroids or splenectomy)
- Chronic: rarely resolves spontaneously (Initial treatment: high dose prednisone, IV immunoglobulin, stem cell therapy, Splenectomy)
9
Q
disorders of platelet function
A
- May be congenital (many possible causes) or acquired (drugs—aspirin or other NSAIDs, clopidogrel/Plavix™—uremia, alcoholism, hypothermia, malnutrition).
- Skin and mucosal bleeding
- Studies show normal platelet levels, but abnormal platelet function or aggregation (specialized studies).
10
Q
platelet consumption syndromes
A
- Thrombotic thrombocytopenic purpura (TTP), rare but often fatal. Occurs in previously healthy patients, between 20-50, more often in women, sometimes in people with HIV.
- Hemolytic-uremic syndrome (HUS) is like TTP but found in children.
- Disseminated intravascular coagulation (DIC) causes generalized bleeding in people with severe underlying illness (e.g., sepsis, cancer).
- Caused by abnormal aggregation of platelets, which both impairs their ability to function normally, AND can cause microvascular infarcts.
- Life-threatening.
- Transfusion, steroids, plasmapheresis.
11
Q
where platelets and coag factors meet
A
- von Willebrand’s factor is not an enzyme, and thus has no catalyzing function.
- What it DOES do is bind: binds to collagen, binds to platelets, and binds to Factor VIII.
12
Q
hemophilia
A
- Classic hemophilia or Factor VIII deficiency. It’s an X-linked recessive mutation, thus affecting men only. About 1 in 10,000 U.S. male births have Hemophilia A.
- A similar syndrome is Hemophilia B. It’s a deficiency of Factor IX, also X-linked recessive, about 1 in 30,000 U.S. male births.
- The hallmark sign is hemarthrosis.
13
Q
bleeding into joints
A
- Can also have epistaxis, intracranial bleeding, hematemesis, melena, microscopic hematuria.
- Tends to present in childhood.
- Symptoms can range from very severe to mild.
- Treatment is Factor VIII (or XI).
14
Q
vitamin K deficiencies
A
- Symptoms are typical of bleeding disorders: petechiae and/or purpura, mucosal bleeding.
- These are the most common acquired coagulopathies.
- It’s a real vitamin (actually a group of vitamins), found in leafy green vegetables. It’s also in vegetable oils, but at low (i.e., nontherapeutic) levels.
- Vitamin K works by modifying certain proteins, preventing them from degradation.
- These include several elements of the coagulation cascade, including prothrombin, Protein C and Protein S, and Factors VII, IX, and X.
- May be due to poor diet, liver failure, malabsorption, malnutrition, or use of broad-spectrum antiobiotics (e.g., sulfanomides).
- Lab findings: prolonged PT, sometimes prolonged PTT. Normal fibrinogen, thrombin time, and platelet count.
- Treatment: the underlying cause (which is usually obvious).
- Can give parenteral vitamin K.
- Can give plasma to treat acute bleeding.
- Address malnutrition and malabsorption.
15
Q
How clinicians prevent VTE
A
- Put patients on “baby aspirin” (81mg chewable daily), to reduce the risk of inappropriate platelet aggregation (inactivates COX).
- Among higher risk patients, more potent anti-platelet drugs may be indicated: clopidogrel/Plavix™ (blocks ADP receptor), or abciximab/Reopro™ (blocks gpIIb and gpIIIa ).
