Coagulation

Question 1

Primary Hemostasis:

• Goal?
• 4 step process?
• Plt granules contain? Roles of each?
• Linker molecule? Attaches to what?
• Platelet structure: Discoid cell with? (2) Nucleus? Maturation takes? Circulate? 3 types of granules? Contents of each?
• Function: Adhesion to? Activation via? Aggregation to form? Provide what for thrombin?

Answer 1

• Make initial weak plug
  1.) Vasoconstriction 2.) vwf line rupture on sub endo collagen 3.) plt’s use GP1B for adhesion to vwf (from endo) 4.) plt’s degranulate with increased expression of GP2B3A for fibrinogen to link
• ADP (help express GP23A) and TXA2 (incr. agg)
• Fibrinogen; GP2B3A
• granules and mitochondria; no; 4-5d; 9-10d
  Dense = ATP,ADP, Seratonin, Ca2+; alpha = fibrinogen, f5, vwf; lysosomal = acid hydrolases
• subendothelium; cytosekl change and release granules; plug; phospholipid

Question 2

Primary Hemostasis:

• Endothelium releases what with expression thrombomodulin (co factor)? Activates what?
• Thrombin, ADP, Epi, TXA2 increase what? Ca2+ activates what?
• Disorders due to what? (3) Common signs? (3)
• Decreased production causes? (7)
• Increased destruction due to? (3)
• Increased sequestration? (1)
• Important screening? (4)
• Test for thrombocytopenia? Plt dysfunction? Hemophilia? F7 defic? Dys. fibrin? Hypo fibrin?

Answer 2

• Heparin like molecule; Protein C&S
• Expression of GP2B3A; Phospholipase A
• Decreased production, incr. destruction or sequestration; bruises/ bloody membranes
• BM disorders, MDS, leukemia, MF, TB, Chemo, folate/B12 defic.
• ITP; Acute in kids or chronic in adults
• TTP
• Bleeding pattern, opportunity to bleed a lot, family Hx, multiple sites
• Plt count, bleeding time, APTT, INR/PT, TCT, fibrinogen test

Question 3

Primary Hemostasis Disorders:

1. ) ITP: Autoimmune production of? Digested where? Sometimes related to? Cross placenta? Plt count? PT/PTT? Bone Marrow? Treatment? (3)
2. ) VW Disease: Only effects primary hemo? Why? Treatment? Does what? Only works for? Why?
3. ) TTP: Deficient in what enzyme? Role? Leads to? RBCs? Pulled out where?
4. ) Bernard Soulier: Deficiency? Which decreases?
5. ) Glanzmann: Deficiency? Decreases what?
6. ) Uremia: Decreases what? (2)

Answer 3

1. ) IgG against plt’s; spleen; Lupus; Yes IgG; Low; normal; Incr. mega; Cortico, IVIG, splenectomy
2. ) No; vwf carries factor 8; DDAVP (arg. vaso) increases release of vwf; type 1; type 2/3 have qualitative problem
3. ) ADAMSt13; chops down vwf; microthrombi in vessels (microangiopathic); schistocytes; spleen
4. ) GP1B; Adhesion
5. ) GP2B/3A; aggregation
6. ) Adhesion and aggregation

Question 4

Secondary Hemostasis:

• Goal? Built on? Cascade generates what? Which does what? How?
• Factors produced where? What form?Activation requires? (3)
• Clinical features? Warfarin effect? Heparin effect?
• Roles of thrombin? (3) Initiated by?
• Vitamin K role?
• TT test effected by?
• Thrombin activates plt’s to release? (3)
• Exposed what leads to coag process? (3)

Answer 4

• Stabilize weak plug; fibrinogen; thrombin; converts fibrinogen to fibrin; cross linked to make thrombus
• Liver; inactive state; activating substance, surface of plt; calcium from plt
• PT which measures common and extrinsic
• PTT which measures common and intrinsic
• Cleave F-gen, activate 5,8, 11, 13, C, S, cleaves PAR; exposed tissue factor
• Gamma carboxy of 2, 7, 9, 10, C, S
• Fibrinogen
• ADP, Vasoactive amines TXA2
• Tissue factor, collagen, - charged surfaces

Question 5

Secondary Hemostasis:

• Regulatory pathways: 1.) Endothelium in tact inhibits? 2.) Protein C: Activated by? Cleaves? Cofactor? 3.) Antithrombin 3: Binds? Inactivates? 4.) Fibrinolytic: Plasminogen to? By? Acts on? Leads to? Can be inhibited by?
• Tests: 1.) PTT: What added to citrated plasma? (2) Normal? Useful for? Sensitive to?
  2. ) INR/PT: Added to citrated plasma? (2) Normal? >5? t? (2)

Answer 5

1. ) Coagulation
2. ) Thrombin; 5A, 7A; Protein S
3. ) Heparin and Thrombin to inactivate them; 9,10, 11, 12 as well
4. ) Plasmin, tpA; Fibrin; D dimers; a2 antitrypsin
5. ) Phospholipid/activating agent;

Question 6

Secondary Hemostasis Disorders:

1. ) Hemo A: Factor involved? Pheno? Labs? Gene?
2. Hemo B: Factor involved? Pheno? Labs? Gene?
3. ) Hemo C: Factor involved? Pheno? Labs? Gene?
4. ) VWF: Factor involved? Pheno? Labs? Gene?
5. ) F7 Def.: Factor involved? Pheno? Labs? Gene?
6. ) Acquired F8: Factor involved? Pheno? Labs?
7. ) Liver disease? Factors? Tests? Check? What is decreased?
8. ) Vit K defic: Factors? How? Labs?

Answer 6

1. ) F8; bleed into joints/soft tiss; High PTT; X linked
2. ) F9; bleed into joints/soft tiss; High PTT; X linked
3. ) F11; present post-op; high PTT; AR
4. ) T1 = deficiency; bloody membranes, skin, GI; high BT; High PTT; Low F8; AD
5. ) F7; Similar to hemo; High PT; AR
6. ) Ab against F8; muscle bleed; High PTT; mix test
7. ) F5, Vit K factors, fibrinogen; High PT/PTT; Vit k levels; Epoxide reductase (activates vit k); factors
8. ) F2,7,9,10; Take ab’s, kill gut flora; high PT/PTT

Question 7

Secondary Hemostasis Disorders:

9. ) DIC: Factor involved? Pheno? Labs?
10. ) APS: Cause? Test? Treatment?
11. ) AT3/Protein C/s defic: Recurrent? Genetics?
12. ) F5 Leyden: Factor involved? Leads to?
    - PT more prolonged than prolongedPTT? (3)
    - PTT more prolonged than prolonged PT?
    - Mix test: Corrects at 0 hours? Not? Still good after 2 more hours? Not?
    - DIC caused by? (5)
    - Lupus anticoag: IgG? PTT? Why? Test?

Answer 7

9. ) F8,5,fibrino, plts, coag cascade activated in vasc., Low fib-gen/plt; high PTT/PT/TT/d-dimer
10. ) Lupus; IgG against phospho; High PTT; viper
11. ) Venous thrombi; AD (all)
12. ) F5 mutated; not inact. by protein c; hypercoag
    - Liver, Vit K, warfarin
    - DIC
    - F defic, Lupus; F defic; Acquired hemo disease
    - Trauma, septic, APL, burn, drug reaction
    - binds plt membrane; High (no phospholipid on plt available); viper venom test helps determine

Question 8

Thrombosis:

• Def? Most common location? 3 risk factors?
  1. ) Disruption of flow: Due to? (2) Causes? (3)
  2. ) Endo damage: a.) Barrier to block? (2) b.) Loss of cytokines? (3) Block? c.) Endo makes what to destroy coag factors? To activate C? Disease? (2)
  3. ) Hypercoagulative state: Genetics? (2) Leads to one of two problems? (2) Present with?
• Arterial clotting: What is important? Therapy?
• Venous clotting: More important? Therapy?
• Virchows triad? Caused by?

Answer 8

• Intravascular clot; disrupted flow; endothelial danmage; hyper coag state
• Stasis or turbulance; A fib, aneurism, immob.
• Subendo collagen/TF; NO,PGI2, AT3; coag; TpA (p-gen to p) Thrombomodulin; high homocysteine, artherosclerosis
• Inheritied or acquired; excess procoagulants; defective anti coagulants; recurrent DVT’s
• Platelets; antiplatelet therapy
• Clotting factors; anticoagulants
• Altered vessels: Inflamm damage, hypoxia
• Venous stasis: Reduced flow, immobility
• Altered coag: Inflam stimuli.,

Question 9

Thrombosis:

• Risk factors for VT? (7)
• Acquired ex? (3)
• Inheritied ex? (2)
• Presentation? (2) Symptoms of each?
• Diagnosis? (3)
• Treatment: Acute? Chronic? Hep acts on?
• Clues of hereditary disorder? (4) Most don’t lead to? Increases risk? Contraindicated?
• Acquired hyper coag state: How many? Used?
  1. ) Antiphospholipid Ab syndrome: Problems? (2) Thombi where? (2) Age? Vascular bed? Often started by? (3) Related disease? Sign? Treatment?

Answer 9

• Trauma, immobility, obesity, estrogen, pregnancy, malignancy, age
• Incr. factors, hema disorders, DIC
• F5 leyden, Prothrombin mutation
• Elevated D Dimer, leg/ lung imaging
• Heparin; Warfarin; 12a, 11a, 9a, 7a, 10a, 2a
• s; venous and arterial; Any; Any; Drug exposure, infection, acute illness; Lupus; Thrombocytopenia; ASA, War, Hep

Question 10

Thrombosis Hereditary Diseases:

1. ) Lack of protein C or S: Genetics? Normal function? Risk of necrosis? Free protein S in blood? Test for what with Protein C?
2. ) F5 Leyden: Normally cleaved by? But? Genetics? Type of resistance? 1 allele? 2? OC?
3. ) Prothrombin 20210A: Mutation in? Increases? How common? Leads to? But?
4. ) Antithrombin 3 Defic: Usually activated by? But now? Regulates what normally? Kidney disease? Type 1? Type 2?

Answer 10

1. ) AD; Inactivate F5 and F8; yes; correlates with risk; activity not levels
2. ) Proteins C, S; now mutated; AD; APC; not too bad; increased risk, even higher risk
3. ) Prothrombin; Thrombin; 2-3% caucasians; venous thrombi; most don’t clot
4. ) Heparin; mutated; Major regulatory protein (2,9,10); yes; low level of protein; low activity of protein

Question 11

• Zymogens/enzymes?
• Cofactors?
• Creates hard clot?
• Ex starts with?
• In starts with?
• Tenase complex?
• Prothrombinase complex?
• Common pathway?
• Natural anticoagulants?
• Initiates clotting via exposure?
• Roles of thrombin?
• Contact Activation?

Answer 11

• 12, 11, 10, 9, 7, 2, 13
• TF, 8, 5
• 13
• TF exposure on fibroblast
• Charged surfaces
• 9, 8, Ca, phospholipid surface
• 10, 5, Ca, phospholipid surface
• 10, 5, 2, 1, 13
• C, S, TFPI, antithrombin 3, thrombomodulin
• TF
• Cleave fibrinogen, 5, 8 activiation; Cleave PAR1 to activate platelets; activate 11, 13; Protein C to APC
• 12, 11, HMWK, KK

Question 12

• Anticoagulation:
  1. ) TF pathway inhibitor? (2)
  2. ) Anti-thrombin 3? Enhanced by?
  3. ) Protein C?
  4. ) Fibrinolysis?
• Pharm: Hep binds? LMW binds?

Answer 12

1. ) Binds TF-10a-7a complex (10 to 10a and 9 to 9a); binds 10a
2. ) Binds 10a, 11a, thrombin, 12, 9; heparin
3. ) Thrombin and thrombomodulin cleave PC to APC; APC-PS cleaves 5a and 8a
4. ) tPA turns plasminogen to plasmin; tpa blocked by PAI1
   - Antithrombin3 and thrombin
   - Only binds anti thrombin 3