Hematology Coagulation

bone marrow 150-300K 8-12 day lifespan spleen sequester up to 1/3 small and positioned close to vessel wall

arrest of bleeding

vasculature platelets blood proteins: clotting factors

vascular spasm plt plug: primary coagulation and fibrin: secondary fibrinolysis

GpIIb-IIIa thrombin TXA2 ADP GpIb

attached activated platelet to vWF

links platelets together (plug)

trauma surgery plaque dislodgnement micro injury

local smooth muscle reduce bloood flow to area functions 1. decrease blood loss 2. keep procoagulants in affected area clotting factors fibrinogen vWF fibronectin

clotting factors 1-13 fibrinogen vWF fibronectin

3 steps: adhesion, activation, aggregation 5 min begins with plts coming in contact with vessel wall positive FB loop

1. adhesion: injury exposes collagen= plts adhere to collagen via GpIa-IIa and GpVI then vWF synthesize/released from plasma goes to injuried tissue and binds GpIb on plt: ANCHORS it to subendothelium 2. activation: exposed collagen activates plts with release: ADP and TXA2> activates more plts and aggregation occurs also release: fibrinogen, fibronectin, vWF, factor 4, plt growth factor plts get sticky and express glycoproteins on surface 3. aggregation GpIIb-IIIa receptor complex link plts together> PLUG ADP and TXA2 are required to configure the complex to accept fibrinogen

1. adhesion: injury exposes collagen= plts adhere to collagen via GpIa-IIa and GpVI then vWF synthesize/released from plasma goes to injuried tissue and binds GpIb on plt: ANCHORS it to subendothelium 2. activation: exposed collagen activates plts with release: ADP and TXA2> activates more plts and aggregation occurs also release: fibrinogen, fibronectin, vWF, factor 4, plt growth factor plts get sticky and express glycoproteins on surface 3. aggregation GpIIb-IIIa receptor complex link plts together> PLUG ADP and TXA2 are required to configure the complex to accept fibrinogen

1. adhesion: injury exposes collagen= plts adhere to collagen via GpIa-IIa and GpVI then vWF synthesize/released from plasma goes to injuried tissue and binds GpIb on plt: ANCHORS it to subendothelium 2. activation: exposed collagen activates plts with release: ADP and TXA2> activates more plts and aggregation occurs also release: fibrinogen, fibronectin, vWF, factor 4, plt growth factor plts get sticky and express glycoproteins on surface 3. aggregation GpIIb-IIIa receptor complex link plts together> PLUG ADP and TXA2 are required to configure the complex to accept fibrinogen

vWF platelet plug step 1 activation

produce FIBRIN

3 7

PT INR

warfarin

EXTRINSIC

8 9 11 12

PTT and ACT

heparin

1 2 5 10 13

2 7 9 10

injury tissue factor 3 released activates 7 activates 10 (with Ca+) prothrombinase (prothrombin activator) and phospholipid activate THROMBIN 2a (remember prothrombin=2 and THROMBIN=2a) proceed to FCP 15 seconds

contact activation pathway, 6 min blood trauma, collagen exposure > activates 12 activates 11 (req: HMW kinnogen…and accelerated by prekallikein) activates 9 8 and 9 activates 10 prothrombin activator and phospholipids activate thrombin 2a proceed to FCP

begins with: prothrobinase (prothrombin activator) converts prothrombin 2 to thrombin 2a thrombin 2a changes fibrinogen >>> fibrin monomer (with Ca+) >> fibrin fibers after platelets aggregate> FIBRIN is added to the platelet plug then FIBRIN STABILIZING FACTOR 13a >> facilitates cross links fo fibrin fibers = CLOT

vasodilation and washout of ADP and TXA anti thrombin inactivates thrombin 2a and 9-12a tissue factor inhibitor neaultralized TF protein C and S will inhibit 5a/8a

mechanism to breakdown clot plasminogen: synthesized in liver, in clot but dormant until activated leads to plasmin > degrades FIBRIN how to activate plasmin: 1. injured tissue released tissue plasminogen active TPA over period of days- major mechanism 2. urokinase (kidneys)- minor mechanism plasmin cuts fibrin>> fibrin degradation products - measured by DDIMER turn off: once clot is gone: 1. TPA inhibitor: inhibit plasminogen so no more plasmin 2. alpha 2 anti plasmin inhibits plasmin

plasmin

plasminogen TPA urokinase

normal 25-32 seconds therapeutic HEPARIN: 1.5-2.5x normal

normal: 12-14 seconds WARFARIN; 2-3x normal: takes several days

normal 90-120 seconds heparin and cardiopulmonary bypass

normal 1 warfarin goal 2-3x normal

fibrinolysis; degradation products if increased: thrombus is likely present somewhere diff dx: DVT, PE, DIC normal under 500

antithrombin

binds to antithrombin and increases its anticoaguabilty by 1000 thus inactivating thrombin and 9, 10, 11, 12 also inhibit plt function

>400

yes, does not cross placenta

hemorrhage HIT allergy hypotension

neuro sx HIT regional

protamine 1mg per 100 units of heparin careful for adverse efffects

hypotesenion allergy Phtn

inhibit vit K epoxide reductase complex 1: inhibit inactive vit K to become active vit K thus indirectly blocking the vit K dep factors: 2, 7 9, 10 and protein C and S

no emergent: 10-20 vit k emergent: 1-2 units FFP

diet abx malabsorption disease hepatocellular neonates exogenous vit K: phytonadione 10-20 mg, give 1mg/1min risks

PTT and bleeding time

VWD: most common inherited plt function disorder plt # normal but wont function vWF: platelet plug step 1 of adhesion; anchors plt to vessel wall and also carries inactive factor 8 in plasma I: mild to moderate DECREASE # amount of vWF >>> desmopressin (ADH) and cryo II: normal amt; DOESNT WORK >> CRYO: contains 8, 13, fibrinogen, vWF…or FFP: contains all clotting factors but not first choice III: severed DECREASE AMOUNT vWF>> first line: purified 8-vWF concentrate, cryo, FFP (NOT desmo)

VWD: most common inherited plt function disorder plt # normal but wont function vWF: platelet plug step 1 of adhesion; anchors plt to vessel wall and also carries inactive factor 8 in plasma I: mild to moderate DECREASE # amount of vWF >>> desmopressin (ADH) and cryo II: normal amt; DOESNT WORK >> CRYO: contains 8, 13, fibrinogen, vWF…or FFP: contains all clotting factors but not first choice III: severed DECREASE AMOUNT vWF>> first line: purified 8-vWF concentrate, cryo, FFP (NOT desmo)

VWD: most common inherited plt function disorder plt # normal but wont function vWF: platelet plug step 1 of adhesion; anchors plt to vessel wall and also carries inactive factor 8 in plasma I: mild to moderate DECREASE # amount of vWF >>> desmopressin (ADH) and cryo II: normal amt; DOESNT WORK >> CRYO: contains 8, 13, fibrinogen, vWF…or FFP: contains all clotting factors but not first choice III: severed DECREASE AMOUNT vWF>> first line: purified 8-vWF concentrate, cryo, FFP (NOT desmo)

VWD: most common inherited plt function disorder plt # normal but wont function vWF: platelet plug step 1 of adhesion; anchors plt to vessel wall and also carries inactive factor 8 in plasma I: mild to moderate DECREASE # amount of vWF >>> desmopressin (ADH) and cryo II: normal amt; DOESNT WORK >> CRYO: contains 8, 13, fibrinogen, vWF…or FFP: contains all clotting factors but not first choice III: severed DECREASE AMOUNT vWF>> first line: purified 8-vWF concentrate, cryo, FFP (NOT desmo)

8, 13, fibrinogen, vWF

all clotting factors

increase PTT

hemophilia A and B increased PTT (intrinsic bc factor 8 and 9) A: factor 8 def males spont bleed into joints, muscle, organs usually more severe than B B: factor 9 def severe bleeding, thromboembolic complications anesthesia consideration T/C give factor 8/9 concentrate prior to sx FFP, cryo TXA or aminocaproic acid

disseminate intravascular coagulation disorganized clotting and fibrinolysis >>> simulataneous hemorrhage and system thrombosis underlying disorder >> systemic activation of coagulation >> increase fibrin formation>>microvascular thrombosis >> organ failure >>consuption of platelets, clotting factors, fibrinogen >> bleeding labs increase: PT, PTT, DDIMER decrease: plt, fibrinogen sx: ecchymossi, petechia, bleeding risk factors: sepsis, OB, malignancy how to treat: underlying cause supportive: fluids, FFP, cryo, plt, LMWH

disseminate intravascular coagulation disorganized clotting and fibrinolysis >>> simulataneous hemorrhage and system thrombosis underlying disorder >> systemic activation of coagulation >> increase fibrin formation>>microvascular thrombosis >> organ failure >>consuption of platelets, clotting factors, fibrinogen >> bleeding labs increase: PT, PTT, DDIMER decrease: plt, fibrinogen sx: ecchymossi, petechia, bleeding risk factors: sepsis, OB, malignancy how to treat: underlying cause supportive: fluids, FFP, cryo, plt, LMWH

disseminate intravascular coagulation disorganized clotting and fibrinolysis >>> simulataneous hemorrhage and system thrombosis underlying disorder >> systemic activation of coagulation >> increase fibrin formation>>microvascular thrombosis >> organ failure >>consuption of platelets, clotting factors, fibrinogen >> bleeding labs increase: PT, PTT, DDIMER decrease: plt, fibrinogen sx: ecchymossi, petechia, bleeding risk factors: sepsis, OB, malignancy how to treat: underlying cause supportive: fluids, FFP, cryo, plt, LMWH

disseminate intravascular coagulation disorganized clotting and fibrinolysis >>> simulataneous hemorrhage and system thrombosis underlying disorder >> systemic activation of coagulation >> increase fibrin formation>>microvascular thrombosis >> organ failure >>consuption of platelets, clotting factors, fibrinogen >> bleeding labs increase: PT, PTT, DDIMER decrease: plt, fibrinogen sx: ecchymossi, petechia, bleeding risk factors: sepsis, OB, malignancy how to treat: underlying cause supportive: fluids, FFP, cryo, plt, LMWH

under normal circumstance: antithrombin inhibits thrombin 2a thus limits size of clots now if deficient>> RISK CLOTS and unresponsive to heparin tx: AT concentrate and FFP

normally: protein S is cofactor to protein C: inhibits 5a/8a to prevent or limit clot so if deficient>> hypercoagulable >> THROMBOSIS TX: 1st heparin then warfarin

resistance to anticoagulation effect of protein C only tx if thromboembolism and use anticoag

effects erythrocytes glutamine triggers: pain, hyPOthermia, hypoxia, ACIDosis, dehydration anes: hydrate, pain control, normotherm, acid base balance dot go above hgb 11