Hemostasis in the Surgical Patient

1
Hemostasis in the Surgical Patient

• Sunil Karhadkar, MD

2
All bleeding (eventually) stops
3
Outline

• Hemostasis
• The Coagulation Cascade
• Surgical hemostasis
• Pharmacology

4
Hemostasis
Primary Hemostasis

• Arteriolar vasoconstriction
• Formation of platelet plug
• Activation of coagulation cascade
• Formation of permanent plug

Secondary Hemostasis
5
(No Transcript)
6
(No Transcript)
7
(No Transcript)
8
The Coagulation Cascade
9
Four reasons for Cell based model

• 1. Congenital deficiency of XII, HMW kininogen
  and pre-kallikrein have prolonged PTT but NO
  BLEEDING PHENOTYPE.
• 2. These components are NOT required for
  hemostasis in vivo
• 3. TF/VIIa activates not only X but also VIII and
  IX
• 4. XI deficiency is not associated with bleeding
  phenotype

10
Cell Based coagulation model

• TF bearing cells
• Adventital cells
• Myo-epithelial cells
• Endothelial cells
• 3 phases
• Initiation
• Priming
• Propagation

11
Initiation

• TF bearing cells exposed to plasma
• VII binds to TF and is activated
• VIIa ? Xa
• TF/VIIa ? IXa
• TF/VIIa/Xa binds Va ? converts Prothrombin to
  Thrombin
• Small amount of Thrombin
• Activate platelets
• accelerant

12
Priming

• Release of granules containing V
• Cleaved to Va
• Formation of VIIIa

Propagation

• Activated platelets rapidly bind V/VIII/IX
• Formation of VIII/IXa complex
• MAJOR activator of X
• Major prothrombin activator

13
(No Transcript)
14
Physiological hemostasis
15
Screening tests for bleeding disorders

• Prothrombin time
• Measures function of VII, X, Prothrombin,
  fibrinogen
• Prolonged when V, VII, X fall below 50
• And when prothrombin level falls to lt30
• Vit K dependent proteins
• Prothrombin, V, VII, X, Proteins C and S
• Warfarin, Liver Failure

16
Screening tests for bleeding disorders

• aPTT
• Detects decrease in
• XII, XI, IX, VIII AS WELL AS
• Fibrinogen, prothrombin, V and X
• Heparin

17
(No Transcript)
18
Anti-Coagulant / Fibrinolytic mechanisms

• Antithrombin III
• Protein C
• Plasmin

19
Hemophilia

• X linked recessive
• Deficiency of Factor VIII
• Degrees of severity
• Mild 5 - 30
• Moderate 2 - 5
• Severe lt2
• Prolonged PTT. Normal PT, vWf, BT

20
Von Willebrand disease

• Most common congenital bleeding disorder
• Bleeding is usually mild
• Etiology of bleeding
• Platelet aggregation
• Major carrier for VIII
• Types

21
Type I vW disease

• Autosomal dominant
• Normal vWF
• Quantitative decrease
• Normal PT
• Mildly prolonged aPTT

22
Rx of vW disease

• DDAVP
• Cryoprecipitate
• Monitor VIII levels

23
DDAVP

• 1-Deamino, 8 D-arginine vasopressin
• Rx for mild Hemophilia A , vW disease
• Increases plasma fVIII, vWf from endogenous
  sorces
• Amount of increase factor transfusion
• Useful for platelet dysfunction secondary to
  aspirin, dextran, ticlopidine
• 0.3- 0.4 mcg/kg
• Onset 30 min, peak 90-120 min

24
Cryoprecipitate

• useful in treating factor deficiency (hemophilia
  A), von Willebrand's disease, and
  hypofibrinogenemia
• uremic bleeding
• Each 5- to 15-mL unit contains more than 80
  units of factor VIII and about 200 mg of
  fibrinogen.
• Because the proteins mentioned previously are in
  relatively high concentration, a smaller volume
  may be given than would be required if plasma
  were used. Cryoprecipitate is usually
  administered as a transfusion of 10 single units.

25
NovoSeven

• Recombinant f VIIa
• Activates X and IX (conversion of prothrombin to
  thrombin)
• Not FDA approved
• Anecdotal miraculous rescues

26
(No Transcript)
27
Heparin

• Blocks Xa by binding to AT-III and thrombin.
• Load 80 mg/kg
• Infusion 18 mg/kg
• Cleared from blood in 6hrs
• Neutralized by protamine
• 100u of Heparin 1mg of protamine

28
HIT

• Heparin induced thrombocytopenia
• Formation of IgG against Heparin- PF4 complexes
• Upto 5 of patients
• Onset 4-5 days, but earlier if prior exposure
• Can occur with flushes, heparin bonded catheters
  also

29
LMW Heparins

• More selective anti-Xa activity
• Less bleeding complications
• Do not affect PT
• Measure anti Xa activity
• lt1 incidence of HIT

30
Enoxaparin

• LMW heparin
• Porcine intestinal submucosa
• Binds to and accelerates AT-III activity

31
Fondaparinux (Erixtra)

• Synthetic pentasaccharide
• 5 sugar AT-III binding site similar to Heparin
• 1000x more potent
• Very low- no incidence of HIT
• Cannot be given in CRI

32
Vitamin K

• Necessary for addition of carboxyglutamate
  residues to the clotting factors synthesized in
  the liver.
• Sites of Calcium binding
• Prothrombin, VII, IX, X
• drugs- cephalosporins, quinolones
• 5mg iv slowly corrects deficit in 6 hrs
• 10-25 mcg /day sq or im x 3days

33
Warfarin
Karl P. Link
34
DIC

• Consumption coagulopathy
• Systemic thromb-hemorrhagic disorder
• Etiology
• Gram negative sepsis, crush injuries, amniotic
  fluid embolism, hemolysis, massive transfusion
• Activation of clotting and fibrinolysis
• Microvascular thrombosis, sequestration of
  platelets

35
DIC

• Low fibrinogen
• High FDP
• Low platelets
• Elevated D-dimer

36
Surgical hemostasis
37
Stopping the bleeding

• Direct pressure.
• More direct pressure. Pack. Pack. Pack.
• Electrocautery.
• Ligate vessel

38
Methylcellulose

• Gelfoam
• Absorbable
• Liquefies in 2-5 days
• Serves as a scaffold for coagulation

39
Oxidized regenerated cellulose

• Surgicel
• Binds platelets and chemically precipitates fibrin

40
Microfibrillar collagen

• Decellularized bovine source
• Stimulates latelet adhesion
• Stops venous ooze
• Absorbed in 90 days

41
Thrombin Gelfoam CaCl

• Thrombin for cleavage/activation
• Gelfoam as matrix
• Very useful in vascular surgery

42
Fibrin glue

• Tiseel
• FDA approved in 1998
• Concentrated fibrinogen and f VIII
• Thrombin and calcium
• Aprotinin to prevent clot dissolution
• Takes time to prepare
• Good for diffuse oozing, needle punctures,
  parenchymal injuries