Coagulation

Front 1

hemostasis

Back 1

-injury to vessel wall causes collagen to be exposed
-initial response is vascular constriction
-plts adhere to collagen (mediated by GPIa/IIa and by binding of plt surface receptor BP Ib/Ix/V) complex to VWF
-this leads to activation of plts by thrombin
-plts relase ADP and TXA2
-aggregation occurs at G2b/IIIA receptors --> plt plug --> fibrin mesh forms

Front 2

dissolution of clot occurs thorough...

Back 2

-the cleaving of plasminogen to the active plasmin which then cleaves fibrin to fibrin split products

Front 3

Historical info

Back 3

1. pts age, sex, ethinicity, Fh
2. any association with drugs, trauma, surgery
3. time of onset and course of bleeding
4. site or sites of bleeding?
5. capillary bleeding (petechiae) vs larger vessel bleeding (echymoses, pupura, hematoma)
6. easy bruising? - how easy? where? how many? how large? how frequent?
7. epistaxis? gum bleeding? Menorrhagia? GI/GU bleeding?
8. does pt have ssx of liver dz?
9. is there a reason why the pt should be vit K deficient

Front 4

Joint bleeds and soft tissue/muscle bleeds

Back 4

-more commonly seen in factor deficiencies such as hemophilia

Front 5

plt antagonists

Back 5

1. ASA
2. NSAIDS
3. Alcohol
4. Antihistamines
5. Bblockers
6. NItrates
7. Calcium blockers

Front 6

screening tests of coagulation

Back 6

1. PT: the extrinsic pathway (factors VII, X, V II), good to monitor coumadin, must use INR
2. aPTT: intrinsic pathway (factors XII, XI, IX, VIII or contact factors)
3/ TCT: final common pathway
4. Bleeding time

Front 7

Mixing studies

Back 7

-first test to run after getting elevated PTT
-mix 50% pts plasma with 50% nml pooled plasma
-if results normalize it means a factor deficiency
-if results stay prolonged it means that there is a factor inhibitor
-if results normalize immediately but then prolong after 60 min it can indicate a factor VIII inhibitor

Front 8

thrombin clotting time

Back 8

-add thrombin to citrated plasma +/- calcium and measure rate of conversion of fibrinogen to fibrin
-prolonged by: heparin, low or absent fibrinogen, abnml fibrinogen, high levels of fibrin, paraproteinemia

Front 9

The bleeding time

Back 9

-a measure of primary hemostasis
-done by making a uniform cut and keeping track of time until bleeding ceases
-can be affected by: plt count <100,000, plt function, VWF abnormalities

Front 10

Coumadin OD intervention and tx

Back 10

1. stop coumadin
2. give vit K replacement: PO, IV, SC - NOT IM
3. transfusion of FFP which contains the Vit K dependent factors
4. cryoprecipitate contains factor II

Front 11

Thrombocytopenia clinical effects

Back 11

-nml plts count (140,000 - 400,000)
-increased bleeding time (<100,000)
-spontaneous bleeding (<10,000)

Front 12

dysfunctional plts

Back 12

-nml plt number but prolonged bleeding time
-drugs: ASA, NSAIDs
-primary hematologic disordeR: myelosysplastic syndrome
-rare inherited disorders: autosomal recessive

Front 13

Immunologic thrombocytopenic purpura (ITP)

Back 13

-can be caused by:
1. disease with immune component
2. drugs
3. infx
4. pregnancy
5. idiopathic

Front 14

The contact factors

Back 14

-factor XII, high molecular weight kininogen, prekallikrien
-interactions with the complement and fibrinolytic systems
-deficiencies of these factors do not result in bleeding problems, despite the fact that they prolong the PTT

Front 15

Factor XI deficiency

Back 15

-prolongs only the PTT
-clinicaly variable bleeding problems
-history may reveal no bleeding!
-inherited form transmitted as an autosomal recessive trait. Increased prevalence in Jewish pop

Front 16

Factor IX deficiency

Back 16

-Vit K dependent
-prolongs only the PTT
-hemophilia B
-an x-linked recessive inherited disorder
-range of severity of bleeding symptoms from very severe to mild
-can treat with factor IX concentrates

Front 17

Factor VIII deficiency

Back 17

-coagulation co-factor which accelerates activation of factor X by factor IXa
-hemophilia A: x-linked recessive
-clinically identical to hemophilia B
-can also have low VIII due to VWD: autosomal dominant
-prolongs only the PTT

Front 18

Deficiencies of factor II (prothrombin), VII and X

Back 18

-associated with liver disease and Vit k deficiency

Front 19

Fibrinogen deficiency

Back 19

-when seen think DIC
-also seen with severe liver disease
-can be see nwith certain drugs
-rare
-prolongs PT, PTT and TCT

Front 20

The fibrinolytic system

Back 20

-degradation of fibrin is primarily a function of plasmin
-plasmin is activated from plasminogen by tissue plasminogen activator
-plasmin "digest" fibrin multimers leaving fibrin pieces "D-dimers"

Front 21

Sepsis

Back 21

-treat with abx
-treat the coagulopathy:
-transfuse plts to keep count >50,000
-transfuse cogaulation factors by giving FFP
-give fibrinogen by infusing cryoprecipitate
-anticoagulate using heparin infusions

Front 22

Von Willebrand Disease (VWD)

Back 22

-a family of disorders characterized by deficient of defective VWF
-the MOST COMMON inherited bleeding disorder
-autosomal dominant
-VWF serves 2 impt functions:
1. the carrier protein for factor VIII
2. the ligand that bins to the GP1b receptor on plts to initiate plt adhesion to collagen on damaged endothelium

Front 23

VWD mild mucocutaneous bleeding manifestations

Back 23

1. bruising
2. epistaxis
3. menorrhagia
4. GI bleeding

Front 24

classification of VWD

Back 24

1. type 1: mild quantitative def and most common
2. Type 3: severe quantitative def and the least common
3. Type 2: a qualitative or dysfunctional/mutant molecule

Front 25

Tx of VWD

Back 25

1. Cryoprecipitate
2. DDAVP: increased plasma VWF by stimulating secretion from endothelium
3. Factor VIII concentrate

Front 26

known clinical associations with thrombotic disease

Back 26

1. immobility
2. obesity
3. smoking
4. cancer
5. pregnancy
6. estrogen therapy

Front 27

Types of thrombosis

Back 27

1. arterial: plt-based thrombus
-plt-VWF interactions critical
-associated with end-stage atherosclerosis
2. Venous: fibrin-based (red) thrombus
-coagulation factors critical
-stasis

Front 28

Defence against thrombosis

Back 28

1. nml blood flow
2. nml vessel wall
-prostacyclin: vasodilator/anti-aggregant
-tissu plasminogen activator: fibrinolytic activator
-heparin-like molecules: antithrombin cofactor

Front 29

Inherited Deficiencies of the Major Physiologic Anticoagulants

Back 29

1. antithrombin III
2.. prot C
3. prot S
-deficiencies results in hypercoaguable states

Front 30

Treatment for DVT

Back 30

1. standard anticoagulant therapy
2. thrombolytic therapy
3. vena caval interruption
4. low molecular weight heparin

Front 31

unfractionated heparin

Back 31

-difficult to monitor
-short half life
-can be used as initial therapy

Front 32

LMWH

Back 32

-more predictable
-less cell binding, less protein binding
-lab monitoring not required (except in kids, obseity, renal failure)
-several types: enoxaparin, daltaparin
-dosage calculated by BW
-complications: bleeding, thrombocytopenia, osteoporosis, can use in preg

Front 33

Coumadin

Back 33

-vit k antagonist
-peak effect reached in ~4/5 days
-monitor with PT
-complications: bleeding, embryopathy, allergies

Front 34

Anti-phospholipid antibody syndrome

Back 34

-hypercoagulability in young women
-PPT elevated, PT mildly elevated, mixing study doesn't correct --> not a factor deficiency, it's a factor inhibitor

Front 35

anti phospholipid antibody

Back 35

-this prolongs the PTT, however it is not a bleeding disorder
-often there are no clinical problems
-some pts may be hypercoagulable and develop clotting problems
-if h/o clotting or repeated preg loss, then it is considered anti-phospholipid syndrome and must be treated

Front 36

Anti-phospholipid antibody syndrome treatment

Back 36

-recent stroke: observation/thrombolytic agent
-future prophylaxis: antiplt agents, anticoagulants
-pregnancies: anticoagulants