Hemostasis, Surgical Bleeding, and Transfusion Patrick Chidi Obasi

Hemostasis Complex process that prevents blood loss from disrupted intravascular space. Major physiologic events: Primary hemostasis Vascular constriction Platelet plug formation Secondary hemostasis Fibrin Formation Fibrinolysis

Vascular constriction Initial vascular response to injury Linked to platelet plug formation Thromboxane A2 (TxA2), Serotonin, 5-hydroxytryptamine (5-HT), Bradykinin

Platelet Plug Formation Conversion of cyclooxygenase to TXA2=> stimulates platelet motility and binding (aggregation) Activated platelets adhere to fibrinogen via GP IIa/IIIb. Plts adhere to von Willebrand factor on exposed collagen via glycoprotein (GP) Ia/IIa receptor Adhesion results in the release of agonist like epi, collagen, thrombin, ADP, Serotonin Platelet cyclooxygenase irreversibly inhibited by ASA and reversibly by NSAIDs

Coagulation/Fibrin Formation Extrinsic pathway Tissue factor (injured cells) + factor VII Activates factors X and V Converts prothrombin to thrombin Thrombin then converts fibrinogen to fibrin Elevated PT associated with abnormal extrinsic pathway cascade

Coagulation/Fibrin Formation Intrinsic pathway All components intrinsic to the circulating plasma HMW kininogen + factor XII (Hageman factor) bind to exposed collagen Activation of factors XI, IX + VIII => X+V Convert prothrombin (factor II) to thrombin Thrombin cleaves fibrinogen to fibrin Abnormal measured by a PTT

Fibrinolysis Plasminogen level known to rise as a consequence of exercise, occlusion, and anoxia tPA-released from endothelium converts plasminogen to plasmin Plasmin degrades factors V and VIII, fibrinogen and fibrin-leading to lose plt plug

Notes on Coagulation Factors Factor II aka prothrombin Factor III aka antithrombin Heparin binds to AT III Deficiency results in spontaneous thrombosis Treat def with FFP (has AT-III) and then heparin

Notes on Coagulation Factors Factors V-labile factor Factor VI – shortest half life. Begins extrinsic pathway Factor VIII – labile factor -- only factor not synthesized in liver (made in endothelium) Factor X – Convergence point for both pathways Factor XII – aka Hageman factor. Begins intrinsic pathway Factor XIII – Helps crosslink fibrin

Local Hemostasis Goal is to prevent or interrupt the flow of blood from a disrupted vessel that has been incised or transected Digital pressure effective and has adv. of being less traumatic Hemostat, hemoclips, transfixion sutures (prevents slipping) The adventitia and media constitute the major holding forces in a vessel wall

Local Hemostasis Thermal agents: Harmonic scalpel, electrocautery bovie (causes collagen denaturing leading to coagulation) Direct cooling with iced saline causes vessels to undergo necrosis by dehydration and destruction of lipid molecules Chemical agents: epi (induces vasoconstriction), gel foam, surgicel, topical thrombin, fibrin sealant)

Heparin Therapy Potentiates action of AT III Inhibited by admin of protamine (1mg of protamine:100 units of heparin for reversal) Measured by aPTT Want PTT between 60-90 for anticoagulation Does not cross placental barrier Stop 4-6 hours before surgery

HIT/HITTS Due to antiplatelet antibodies (IgG) that results in plt destruction Can cause plt aggregation and thrombosis (“white clot”) Typically seen 5 to 7 days in first exposure May occur within 1 to 2 days in re-exposure Suspected if plt count falls more than 100k or drops by 50% from baseline LMWH (Lovenox) still at low risk Tx: stop heparin, start lepirudin/Hirudin, argatroban, dextran

Coumadin Therapy Inhibits cyclo-oxygenation (decarboxylation) step in Vit K synthesis of coag Effects reversed by Vit K admin Stop 7 days before surgery Measured by INR INR >1.5 – contraind. for surgery INR >1.3 – contraind. for central line placement, perc. needle bx and eye surgery Teratogenic

Warfarin-induced skin necrosis Occurs when pt is placed on coumadin without heparin first Due to short ½ of prot. C and S, which are first to decrease in levels compared with the procoagulants (factors II, VII, IX and X) Above results in relative hyperthrombotic state Tx: Heparin if it occurs, prevent by heparinizing first

Hypercoagulability Leiden Factor Polycythemia vera Resistance to activated prot C and S Spont venous thrombosis Most commoncongenital hypercoagulability disorder Tx: heparin, warfarin Polycythemia vera Defect in plt function Can have thrombosis/bleeding Keep Hct<48 and plts <400 before surgery Tx: ASA

Hypercoagulability AT-III Pts have spont venous thrombosis Heparin does not work Tx: AT-III conc, FFP then followed by Heparin

Hypercoagulability Lupus Anticoagulant (Procoagulant) Antiphospholipid antibodies Prolonged PTT in the face of hypercoag state Dx: Prolonged PTT not corrected by FFP Tx: Heparin, coumadin Acquired hypercoag: Tobacco, malignancy, IBD, infections, post-op state

DVT Stasis, venous injury, hypercoagulability Risk factors include cancer (#1), obesity, varicose veins, history of DVT, immobility Most common site in post-op pt is the pop vein Activated prot C resistance due to factor V leiden def is the most common cause of idiopathic recurrence Dx/Tx:

PE Presents with SOB, tachycardia, hypoxemia, normal or decreased PaCo2 Most common from above knee (iliofemoral region) Dx/Tx Indication for surgical procedure When filters are indicated Pt who have undergone pulm emboletomy Pts with contraindication for anticoagulation PE while on anticoagulant Free floating above knee DVT

PRBC Storage 1 Unit of PRBC has a vol of 250 ml Storage life is about 35 days ↑K+, ↓ pH, ↓ 2.3-DPG level (↓ O2 del capacity), ↑ IL-1, and IL-6 Each unit expected to raise H/H by 1gm/3% Fever without hemolysis is the most common transfusion reaction Acute hemolysis is the most common cause of transfusion related death Hypotension, shock, dyspnea, bronchospasm, dizziness and flushing are sign of hemolysis Tx: Supportive