1. Hemostasis, BLOOD PRODUCTS & TRANSFUSION
M K Alam MS;FRCS
Professor of Surgery

2. 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

3. 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.

4. 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

5. Hemostasis Primary hemostasis: Secondary 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

6. 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

7. 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.

8. Congenital or acquired abnormalities of:
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

9. 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.

10. 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.

11. 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

12. 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.

13. 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

14. 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

15. 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) 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 min.
Hematology consultation -more specialized investigations.

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

17. 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 days

18. 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.

19. Blood Components Packed red blood cells (PRBC) Platelets
Fresh frozen plasma (FFP)
Cryoprecipitate

20. 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

21. 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

22. 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: ml/kg body weight (2-4 units/ patient)

23. Cryoprecipitate Indications for use
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

24. 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)

25. 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

26. 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

27. 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.

28. 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.

29. Thank you!