Bleeding and Clotting - Hubbard Flashcards by Elizabeth Mazza

platelet adhesion is dependent on glycoproteins on platelet surface and is mediated by vonWillebrand factor

activated platelets have storage granules and secrete factors (ADP, serotonin) which recruit other platelets
end result is the formation of a platelet plug which blocks egress of blood from the site of vascular injury

primary hemostasis

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involves the serum coagulation factors which ultimately catalyze the devlpment of fibrin latticework which braces and supports the platelet plug
- serum coagulation factors also function to recruit platelets and amplify both primary and secondary hemostasis

secondary hemostasis

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what ROS are important to ask in a pt with bleeding disorder?

bleeding
bruising
abnormal clotting
recurrent DVT
hx of PE/stroke
fatigue
fever
enlargement of spleen/LN/liver
weight loss
GO bleed
GU bleed -> beware beeturia!

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what should always be considered a cause of petechiae/thrombocytopenia?

medications:

abx (cephalosporin)
H2 blockers
heparin
digoxin

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complication of medical, surgical, obstetrical situations

intrinsic and extrinsic coagulation system are activated with resulting local and general escape of thrombin into the circulatory system, resulting in initial thrombosis
a platelets and clotting factors are depleted, bleeding ensues -> major factor of dz

disseminated intravascular coagulation (DIC)

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what is the tx for DIC?

correction of underlying dz: sepsis, bowel obstruction
heparin (only if thrombosis occurs)
supportive care

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generalized disorder of microcirculation characterized by thrombocytopenic purpura, microangiopathic hemolytic anemia (schistocytes), fluctuating neurological signs, febrility

thrombotic thrombocytopenic purpura (TTP)

- hyaline thrombi which occlude the capillaries of virtually every organ in the body

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MAHA + thrombocytepenia (<50k) + fever + neurologic symptoms

TTP

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MAHA + thrombocytopenia (<50k) + fever + neurologic symptoms + RENAL FAILURE

hemolytic uremic syndrome (HUS)

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what are the two major forms of TTP?

hereditary: ADAMTS13 mutation
acquired: autoAb against ADAMTS13 (linked to infection, malignancy, immune disorders)

No ADAMTS13 = too much clumping

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what is the tx for TTP?

treat the underlying cause
plasmapharesis
nearly 100% mortality if not treated

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very large group of related disease that have decreased platelet adhesion as their hallmark

vonWillebrand disease

- pathologic lesion is decreased or absent vWF

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what is the tx for vonWillebrand disease?

cryoprecipitate (replaces vWF)

- DDAVP (causes release of vWF from endothelium

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defects in platelet function may be seen in what 3 diseases?

uremia: impaired platelet adhesion
dysproteinemias: interference with platelet membrane function
autoimmune disorders: multiple abnormalities

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the only endothelial syndrome associated with hemostatic complications

caused by thinning of vessel walls with telangiectatic formations, AV malformations, and aneurysmal dilations throughout the body
AD inheritance
telangiectasias gradually appear throughout life
epistaxis MC sx

hereditary hemorrhagic telangiectasia

- aka Osler-Weber-Rendu syndrome

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hereditary hemorrhagic telangiectasia is caused by a defect in what gene?

endoglin (CD105) on xsome 9

- membrane glycoprotein strongly expressed on endothelial cells

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what is the tx for hereditary hemorrhagic telangiectasia?

surgery and laser photoablation of telangiectasias of some value
- usually benign clinical course, recurrent bleeds frequent, but death from exsanguination is rare

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recurrent LE thrombophlebitis and DVT, venous insufficiency, chronic leg ulcers
- significantly increased risk DVT in pregnant women (due in part to pregnancy-induces hypercoagulability)

AT-III deficiency

- diagnosed by decreased levels AT-III in serum (<50%)

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what is the tx for AT-III def?

prophylactic w/ anticoagulants
pts w/ DVT should receive heparin, HIGH doses
AT-III replacement therapy is available for pts w/DVT

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protein that inactivates factors V and VIII

protein C

protein that is a cofactor for protein C

protein S

MCC of hypercoagulable state from deficiency of protein C and S is caused by what?

initiation of warfarin therapy

- protein C and S are depleted prior to the other factors, resulting in temporary increase in coagulability

abnormality of what factor, at the binding site for activated protein C

factor V leiden

heterozygotes at increased risk for thromboembolic disease
homozygotes have excessively high risk for thromboembolism

what is the tx for factor V leiden mutation?

no prior episodes: DVT prophylaxis

- prior episodes: consider lifelong anticoagulation

mutation resulting in increased activity for prothrombin and inability to de-activate prothrombin - risk of thrombosis very high!

prothrombin 20210 - aka factor II - combined with facor V leiden, may account for most cases of hereditary thrombophilia

what is the tx of prothrombin 20210 mutation?

same as factor V: - no prior episodes: DVT prophylaxis - prior episodes: consider lifelong anticoagulation

- anticardiolipin Ab syndrome - lupus anticoagulant - false positive VDRL Ab syndrome

antiphospholipid syndrome

what are the assoc features of antiphospholipid syndrome?

- thromboembolic phenomena - miscarriage - thrombocytopenia - cerebral ischemia and recurrent stroke

connective tissue disease (present in >50%, but not required for dx) - **prolonged PTT** - valvular heart disease - coronary artery disease

antiphospholipid synd

what are the three diagnostic tests that Hubbard wants us to know for antiphospholipid syndrome?

1. prolonged PTT 2. lack of correction in mixing studies using NL plasma 3. neutralization of inhibitor with excess phospholipid NOTE: multiple positive tests over 3-12months required to make dx

what test may be more specific than PTT for antiphospholipid syndrome?

dilute Russell Vwhatiper venom time (DRVVT)

what is the tx for antiphos synd?

lifelong anticoagulation - heparin in pregnancy - hydroxychloroquine in pts w/ APS and SLE

anticoagulation during pregnancy may be accomplished with what in pt with antiphospholipid syndrome?

**subQ heparin** KNOW this

what are the 3 elements of virchows triad?

1. vessel wall damage 2. altered blood flow (stasis) 3. hypercoagulability

what are the 4 main INHERITED thrombotic disorders that Hubbard wants us to know?

- antithrombin III def - protein C and S def - factor V leiden mutation - prothrombin 20210 mutation

what are the 3 main ACQUIRED thrombotic disorders that Hubbard wants us to know?

- protein C and S def - dysfribrinogenemias - antiphospholipid synd

PE finding, pain in calf or popliteal area on dorsiflexion of foot - **beware lots of false positives and negatives

Homans sing

PE finding, pain typically caused with compression of the calf against the tibia but not when squeezing the calf itself - neither sensitive not specific for DVT

Moses sign | - aka Bancrofts sign

pain with percussion of the anteromedial tibia | - not sen/specific for DVT

Lisker's sign

BP cuff applied to mid-calf and pain elicited with inflation to 80mmHg - not sen/specific for DVT

Lowenberg's sign

veins of affected leg distended in comparison to non-affected leg - not sen/specific for DVT

unilateral superficial venous distention

- clinical sx/sy of DVT - alternative dx less likely than DVT - HR 100bpm - immobilization (>3 days) or surgery in last 4 weeks - previous hx DVT - hemoptysis - active cancer w/in last 6 months

* *modified wells criteria for DVT** | - KNOW this

- previous PE or DVT - HR 100bpm - recent surgery/immobilization - clinical signs of DVT - alternative dx less likely that PE - hemoptysis - cancer

* * modified wells criteria for PE** | - KNOW this

what is the scoring range for well criteria?

``` 0-1 = low probability 2-6 = intermediate probability 7+ = high probability ```

medical sign involving episodes of vessel inflammation due to blood clot (thrombophlebitis) which are recurrent or appearing in different locations over time (thrombophlebitis migrans or migratory thrombophlebitis)

trousseau's syndrome

what are the 3 main causes of drug-induced hypercoagulability?

1. tamoxifen: SERM that increases risk DVT/PE/stroke 2. bevacizumab: VEGF inhibitor may cause both arterial and venous thromboembolic issues 3. thalidomide, lenalidomide: angiogenesis inhibitors that cause arterial and venous thromboembolic issues

what are the "other" causes of hypercoagulability?

- prolonged sitting - extended travel - heart failure -> major RF for intracardiac thrombi

what are the two examples of synnergistic risk factors for DVT?

- oral contraceptives + heterozygous factor V leiden | - hyperhomocystinemia + heterozygous factor V leiden

what are the pharmacologic and non-pharmacologic therapies that prevent DVT/PE?

- stop smoking | - stop meds that increase risk (oral contraceptives, tamoxifen, megestrol acetate)