Hemostasis, BLOOD

PRODUCTS & TRANSFUSION

M K Alam MS;FRCS

Professor of Surgery

ILOs

• At the end of this presentation students will be able to:

Understand the mechanism of normal hemostasis. Describe disorders associated with coagulopathies. Describe investigations for coagulation abnormalities. Understand about blood donation and red cell serology. Describe the blood components and plasma products. Explain indications and adverse effects of blood

transfusion. Describe the autologous transfusion Describe methods to reduce the need for blood

transfusion

Hemostasis

• Hemostasis is a complex process that prevents or terminates blood loss from a disrupted intravascular space.

• Four major physiologic events: Vascular constriction, platelet plug formation, fibrin formation, and fibrinolysis occur in that general order.

Components of hemostasis

• Vessel integrity, endothelium, subendothelium• Platelets and red blood cells• Pro-coagulant factors (fibrinogen (I), prothrombin (II), factors VII,IX, and X)

• Anti-coagulant factors (plasminogen, protein C, protein S & antithrombin III)

• Calcium• Blood flow, temperature and pH

Hemostasis

• Primary hemostasis: Vasoconstriction and platelets aggregation in response to vascular injury

• Secondary hemostasis: Generation of thrombin and fibrin clot formation at the

site of vascular injury

Normal hemostasis

• Platelets: Endothelial injury→ exposes collagen, which activates

them. Von Willebrand factor (vWF)→ promote platelet adhesion,

platelet aggregation and thrombus formation.

• The coagulation cascade :

• The extrinsic pathway-activated factor VIIa + tissue factor→ IX , X

• The intrinsic pathway- initiated by factor XI to XIa by factor XIIa, .

• The common path- Xa+ Va→ prothromb. to thrombin→ fibrinogen

to fibrin

Anticoagulant factors

• Antithrombin III- inhibits coagulation by binding to clotting factors (e.g., thrombin, factor Xa). Heparin accelerates AT-induced factor inhibition.

• Protein C–protein S system: Activated protein C inactivates factors Va and VIIIa in the presence of protein S.

• Plasmin degrade fibrin, which allows for natural dissolution of a clot. Exogenous streptokinase and urokinase help to activate fibrin-bound plasminogen into plasmin.

Defects of hemostasis

Congenital or acquired abnormalities of:

Platelets -Von Willebrand’s disease, thrombocytopenia, aspirin

Pro-coagulant factors- Vitamin. K dependent factors- II, VII, IX, and X

Anticoagulant factors deficiencies: Protein C and S

Platelet disorders

Thrombocytopenia: < 140,000/μL , increased bleeding <50,000/μL.

• Drug induced:

↓ production: Thiazide, chemotherapy agents, estrogens.

↑ destruction: Heparin- HIT I (non-immune)

-HIT II (heparin-dependent antibodies),

Rifampicin, sulfonamides.

• Dilutional: massive blood transfusion.

• Others: DIC, sepsis, ITP, dialysis.

Platelet disorders

Thrombocytosis: >600,000/μL.

Myeloproliferative disease,

Post-splenectomy.

Increased risk of thrombotic episodes. Aspirin reduces risk.

Platelet dysfunction:

Hereditary (von Willebrand , Glanzmann).

Acquired- aspirin- inhibiting platelet synthesis of thromboxane A2,

uremia, liver dis.

Acquired factor deficiencies

• Vitamin K deficiency : Production of inactive forms of prothrombin, factors VII, IX, and X, and proteins C and S.

• Sepsis- protein C, protein S, and antithrombin III are decreased (microvascular thrombi form).

• Liver disease: Decreased synthesis of clotting factors and inhibitors.

• DIC: Sepsis, extensive trauma, antibody–antigen reactions, malignancies, liver failure, obstetric complications. Inappropriate generation of thrombin within the vasculature → formation of fibrin thrombi, consumption of coagulation factors, particularly fibrinogen, and activation of fibrinolysis

Inherited factor deficiencies

• Hemophilia : Deficiency of factor VIII (hemophilia A) or factor IX (hemophilia B, Christmas disease).

• Diagnosis -by history, elevated PTT, normal PT, & normal bleeding time.

• Treatment: Bleeding (e.g., during a surgical procedure) requires factor VIII replacement. Cryoprecipitate (factor VIII, vWF, and fibrinogen) for hemophilia A . Purified factor IX for hemophilia B.

Hypercoagulable disorders

• Antithrombin deficiency : Autosomal dominant disorder. AT-deficient patients- level restored to > 80% with AT concentrate prior to operation or childbirth.

• Protein C & S deficiency : Factors Va and VIIIa are not adequately inactivated → unchecked coagulation

• Factor V Leiden- a genetic mutation in factor V that renders it resistant to breakdown by activated protein C. Increased risk for thromboembolism.

• Pregnancy, malignancy, estrogen therapy

Preoperative Evaluation of Hemostasis• History: Excessive bleeding after tooth extraction, child

birth, or surgery. Nose bleeds

• Aspirin, NSAID (platelet function) intake

• Warfarin ( Vit. K inhibitor) intake

• Liver disease - ↓production of coagulant factors -clearance of activated anticoagulation factors

• Renal failure diminishes platelets function

• Vit. C deficiency (diet)- lead to defect of subendothelium

• Physical examination: Mucosal bleeding, petechiae, or purpura, splenomegaly

Laboratory Evaluation of Hemostasis

• PT- (11-14 sec.) measures factor VII, factor X, prothrombin/thrombin, fibrinogen, and fibrin. Warfarin and vitamin K deficiency deplete prothrombin; factors VII, IX, and X; protein C and S and prolong the PT.

• INR (International normalized ratio)- measures function of I, II,V,VII, & X. - Monitoring patients on warfarin

• aPTT (partial thromboplastin time) 26-36 sec. Measures above factors and VIII. to XII. -Monitor patients on heparin.

• Normal PT & ↑ aPTT- deficiency of the intrinsic pathway factors.

• ↑PT & normal aPTT- abnormalities of the vitamin K–dependent factors.

• Platelets count- prolonged bleeding time in deficiency.

• Bleeding time - 2.5-9 min.

• Hematology consultation -more specialized investigations.

PT aPTT VII XII XV II (prothrombin) XI Fibrinogen IX VIII X V II Fibrinogen

Blood donation

• Healthy adults.

• 480 ml.

• ABO grouped, Rhesus typed, antibody screened.

• Screened for diseases- HBV, HCV, HIV,HTLV, CMV and others.

• Donated whole blood- collected in an anticoagulant (citrate) and nutrient (phosphate, dextrose & adenine) solution (CPDA).

• Stored- at 4°C, shelf life 35-40 days

RBC serology

• ABO antigens- (carbohydrate) in cell membrane.

• anti-A or anti-B antibodies- in plasma.

• Group O: Both anti-A & anti-B antibody Can only receive O blood.

• Group O: Universal donor. Processing removes plasma, hence reduces antibodies.

• RhD antigens: Positive or negative individuals.

• RhD- negative- do not have anti- RhD.

• Child bearing age female: Not given RhD positive blood to avoid

production of RhD antibodies.

Blood Components

• Packed red blood cells (PRBC)

• Platelets

• Fresh frozen plasma (FFP)

• Cryoprecipitate

Packed red blood cells (PRBC)

• Symptomatic anemia-fatigue, tachycardia, mental sluggishness. (Hb. ˂ 7 g/dl or 7-9 g/dl in cv disease sufferers)

• Acute blood loss.

• Adult infusion rate: 1 unit over 1-3 hours.

• 1 unit of PRBC: increases Hb. by 1Gm.

• Irradiated PRBC (prevent graft-versus-host disease from viable lymphocytes).

- Congenital immune deficiency syndrome,

- Organ and stem cell transplant ,

-- Lymphoid malignancies,

- Active treatment for carcinoma

Platelets

• Normal platelet count 150-400 x10⁹/ L

• Indications for transfusion:

Thrombocytopenia

Platelet-function abnormalities (aspirin)

• 1 unit platelet concentrate increase the circulating platelet

count by about 10,000/L in the average 70-kg person.

• Pediatrics: 1 unit/ 10kg patient weight

Fresh frozen plasma (FFP) Indications

• Multiple/specific coagulation factor deficiency (specific factor not available)

• Reversal of warfarin effect• Large volume (10 units) blood transfusion within few hours• Before any invasive procedures if INR >1.5 • Deficiency of antithrombin III before surgery• Replacement of deficient factor to 25% of normal - adequate

for hemostasis• Dose of FFP: 10-15 ml/kg body weight (2-4 units/ patient)

Cryoprecipitate

• Derived from plasma that has been frozen and then thawed

• Rich source of fibrinogen and factor VIII

• Infused rapidly (10 ml/ min.) in adults

Indications for use

• Bleeding due to fibrinogen deficiency• Factor VIII deficiency, if specific factor not available• Glue to patch dura mater or lacerated liver

Albumin

• Chief plasma protein

• Treatment of shock

• Replace fluid loss in burn

• Oedema due to hypoproteinemia

• Persists in intravascular space for >24 hours

• Free from danger of transmitting diseases (unlike RBC,

platelets and plasma)

Recombinant Factor VIIa

• Treatment of bleeding in hemophiliacs

• Excessive bleeding due to trauma or thrombocytopenia

• Profuse postoperative bleeding due ulcer or inflammatory

bowel disease*

• Complications: thromboembolic, myocardial infarction,

cerebrovascular accidents

Massive blood transfusion

• Definition: “one blood volume” replaced within 24 hours

• Dilutional coagulopathy- prompt clinical/ lab. assessment

• Hematocrit maintained above 25% until bleeding stops

(RBC assist in flow of platelets along vessel wall)

• Platelets maintained >50,000/ml, preferably 100,000/ml

• FFP at 2-4 hours interval - maintain normal INR & PTT

• Cryoprecipitate for low fibrinogen

• If bleeding persists- DIC screen

Adverse effects of transfusion• Acute hemolytic reaction: ABO compatibility, develops within

minutes. Chills, fever, infusion site pain, shock, renal failure. May be fatal.

• Febrile non-hemolytic reaction: Abs in donor plasma react with recipient leucocytes. Mild.

• Allergic reaction to plasma proteins. Urticaria or anaphylaxis.

• Bacterial contamination during collection or storage. Symptoms/signs of sepsis. May be fatal.

• Circulatory overload.

• Transmitted infection.

Blood saving techniques

• Autologous transfusion: Collected from fit patients preoperatively, stored and given to the patient later during surgery, if needed. Not popular.

• Cell salvage: During surgery blood collected from suction, processed by salvage machine, then given back to patient. Appropriate when heavy blood loss. Contraindicated in sepsis or malignancy.

Thank you!