الله بسمالرحيم الرحمن

THE HEMOSTASIS, HAEMORRHAGE &

BLOOD TRANSFUSIONPROF. DR. NAWEL

HUSSEINM.B.,B.Ch, M.S., FRCS (Ed. UK),

MDPROFESSOR OF ONCOSURGERY

HEMOSTASIS Definition: Hemostasis is the physiological process by

which bleeding is controlled. How: It has four components:

Vessel wall vasoconstriction (the first response). Platelet aggregations & adherence. The coagulation cascade converts prothrombin to thrombin to

produce a fibrin clot (see intrinsic & extrinsic pathways). The intrinsic pathway is initiated by exposure of coagulation factors to

subendothelial collagen. Various coagulation factors react to converge on factor X which cleaves pro-thrombin to thrombin.

The extrinsic pathway is activated by tissue factors or glycoproteins. Fibrinolytic system → termination of thrombus propagation. It

depends on four proteins: Plasmin, a serine protease that is produced by the action of thrombin

on plasminogen. It attacks unstable bonds between fibrin molecules to generate fibrin degradation products.

Antithrombin III (deactivates thrombin, Xlla, IXa, & Xa). Proteins C & S (prevent thrombin generation by binding factors Va &

VIIIa). Heparin (potentiates antithrombin III).

HEMOSTASIS

HEMOSTASISLaboratory investigations: Platelet count. Normally

200-400,000/L. (70,0009/L is needed for surgical hemostasis) (<20 ,000/L spontaneous bleeding may occurs).

Blood film → platelet count & their morphology.

Bleeding time (normal bleeding time means normal platelets, normal function, and normal vascular response to injury).

Prothrombin time (PT) → Reflects the extrinsic pathway (I, II, V, VII, X).

Partial prothrombin time (PTT) → reflects the intrinsic pathway (all factors except VII).

Individual clotting factor assays.

Thrombin time (TT) → Rate of conversion from fibrin to fibrinogen.

Fibrin degradation products (released by the action of plasmin and are raised in DIC).

D Dimer test: it is a good negative test to exclude the presence of DVT or pulmonary embolism.

HEMOSTASIS Disorders of hemostasis:

Vessel wall:Hereditary hemorrhagic telangiectasia.

Ehlers-Danlos syndrome. Drugs (e.g. steroids). Sepsis, Trauma, Vasculitis.

Platelets:Normal platelets count is 200,000-400,000/mm³

Thrombocytopenia i.e. platelets count is < 100,000mm³.

Platelets count of 70,000/mm³ is usually adequate for surgical hemostasis.

Spontaneous bleeding occurs if the platelets is < 20,000/mm³

Causes: Congenital platelet disorders. Thrombocytopenia. Myeloproliferative disorders. Drugs (e.g. aspirin).

 

Coagulation abnormalities:Congenital e.g. hemophilia A (factor VIII), hemophilia B or Christmas disease (factor IX), von Willebrand's disease (vWF).

Acquired e.g. DIC, vitamin K (which is produced by gut flora).

HEMOSTASIS

HEMOPHILIA 

Hemophilia A is due to factor VIII deficiency .

Hemophilia B (Christmas disease) is due to factor IX deficiency .

 

HEMOPHILIA A

Sex-linked clotting disorder transmitted by asymptomatic female carrier & manifests only in males.

One-third of patients have no family history.

Cause: Deficiency of factor VIII (but the antigenic activity is normal).

Clinical presentation: The condition usually presents in childhood with: Prolonged hemorrhage after dental extraction.

Recurrent hemarthrosis or muscle hematomas.

Subperiosteal hematomas → hemophilic pseudo tumours.

Investigations:APPT is prolonged ,

PT is normal .↓Factor VIII.Treatment:

Bleeding episodes → factor VIII replacement.

Desmopressin → ↑ intrinsic factor VIII levels three folds .

Immediately before surgery, 5-10 units cryoprecipitate is usually given.

 N.B Surgery can

be carried out if the level is raised to 50-75% of normal value.

HEMOSTASIS

HEMOPHILIA B OR CHRISTMAS DISEASE Transmitted either as autosomal

dominant or autosomal recessive trait Cause : Deficiency of factor IX Clinical presentation: Like hemophilia A. Treatment: Fresh frozen plasma or dried

concentrate of 1X factor.

HEMOSTASISDISSEMINATED

INTRAVASCULAR COAGULATION (DIC)

Causes: Simultaneous activation of both coagulation & fibrinolytic systems → bleeding tendency.

Predisposing factor: Severe sepsis, malignancy, shock, burns, transfusion reactions, eclampsia, amniotic fluid embolus, intra uterine bleeding and leukaemia.

Investigations:Reduced serum fibrinogen levels (<1

mg / ml) .Increased fibrin degradation products.

Treatment:Fluid resuscitation, treat underlying

cause .Correct clotting abnormalities with

fresh frozen plasma, cryoprecipitate, platelet transfusion.

Some advocate the use of heparin to stop propagation of thrombosis, (addition of platelets & clotting factors would ‘fuel the fire’).

HEMORRHAGE

Definition: Hemorrhage means escape of blood outside cardiovascular system e.g. → External bleeding from wounds &

mucous membranes e.g. epistaxis. Bleeding into body cavities or lumen of

hollow organs e.g. hemothorax, hemoperitoneum,

Bleeding into tissue spaces e.g. SC hematoma, bleeding into muscles.

HEMORRHAGE

Sources of bleeding: Arterial bleeding: has the following

characters → Bright red, Occurs in jets synchronous with heart

beats. Stopped by compression or bandage with

pressure exceeding systolic pressure. Venous bleeding has the following

characters → Dark red, continuous, Bleeding from big veins is synchronous

with respiration. Stopped by elevation above the level of

heart.  

Capillary (In the form of oozing from wounds).

HEMORRHAGE Types of hemorrhage according to cause: 

Traumatic: Either direct (including operative trauma) or indirect) → tear of blood vessels bleeding. It is further subdivided into → Primary hemorrhage {at the time of trauma}. Reactionary hemorrhage {within 24 hours after trauma}. It is

either due to displacement of clot or slippage of ligatures. Secondary hemorrhage {Occurs 1-2 weeks after the onset of

trauma & it is secondary to sepsis}. Pathological: Secondary to pathological disease

affecting the vessels) e.g. aneurysm, malignant erosion of blood vessels.

Spontaneous: Due to → Platelets disorders e.g. purpura. Coagulation disorders e.g. hemophilia, ↓VK. Diseases affection the capillary wall or supportive tissue e.g.

scurvy.

Effects of hemorrhage {see hypovolemic shock…mild , moderate & severe shock}: Loss of blood → ↓ Oxygen carrying capacity of blood → anaerobic oxidation of tissue → ↑ lactic acids → metabolic acidosis.

HEMORRHAGEManagement of

hemorrhage:First aid:

Elevation, bandage, tourniquet (TK mark included the time of application should be applied to forehead during transportation of traumatized patients to remind the receiving doctors about the presence of tourniquet).

Oxygen supply if the bleeding is severe.

Ringer lactate solution in ratio 3:1 is given first in resuscitation period.

Blood transfusion if loss is > 30% of blood volume .

Control of bleeding vessels:Direct ligature of unimportant

bleeding vessel .Reconstructive vascular surgery if

the bleeding vessels is important e.g. grafting.

In case of secondary hemorrhage; if control of bleeding point in situ is impossible because of friability of tissue, proximal ligation of feeding vessel is an alternative choice.

Spontaneous hemorrhage: treatment of cause.

CRUSH SYNDROME OR TRAUMATIC ANURIA Cause: Prolonged crushing injury or

tourniquet to limb. Pathogenesis: Prolonged muscle

ischemia → necrosis liberation of acid myohematin blood → blockage of renal tubules → myoglobinuria & anuria.

Clinical features: General: Shock & later on,

manifestations of renal failure & anuria. Local: The affected limb becomes

swollen, muscles are paralysed & pulse is absent.

Urine is acidic with hematuria & albuminuria.

Treatment: Alkalinisation of urine to prevent

precipitation of acid myohematin in renal tubules.

Mannitol infusion to induce diuresis. Anti-shock measures & management of

renal failure if occurs (including dialysis).

BLOOD TRANSFUSION

Indications  :Restoration of Acute Loss .Improvement of O2 carrying capacity

especially when hematocrit value is < 30%.

Correction of coagulopathies e.g. purpura, hemophilia.

To replace infant’s blood in case of erythroblastosis foetalis.

During heart – lung machine. N.B :

HB level of 7-8 mg/dL is adequate for tissue oxygenation in most normo-

volemic patients ;In older patients, & patients with

cardiorespiratory disease, hemoglobin must be kept above 9 mg/dL.

Transfusion of one unit of blood →↑ Hb by about 1g/dL in a 70kg adult.

Chronic anemia secondary to renal disease is usually treated with

erythropoietin 50-100 U/Kg/W SC 3 times rather than with blood transfusion.

BLOOD TRANSFUSION

Donor selection: Aim:

To protect the donor from harm & the recipient from any ill effects of transfusion.

To prevent unsuitable donations from being collected.

Procedure: Educate to make donors excluding

themselves if they are not suitable for donation.

It is not practical to carry out a full medical examination on every volunteer. Therefore we rely upon simple visual assessment by trained medical staff & answers to questions about general health, medical history & medication.

BLOOD TRANSFUSION Donor safety:

Donors must be in good health, within the permitted age range.

Donors are not allowed to give more than 13% of their blood volume, to minimize the risk of vasovagal reactions.

Donation should not render the donor anemic (Before each donation the hemoglobin level is assessed).

Donation must be deferred when it is expected to affect the general health of donors.

  Recipient safety:

Selection of donors & blood screening are important steps to avoid the transmission of infectious agents (Despite careful blood screening tests, infection may still be transmitted; donation during the incubation period of an infection, i.e. during the ‘window period’ of infectivity, before screening tests become positive).

Cross matching test to avoid transfusion of incompatible blood transfusion.

BLOOD TRANSFUSION

Cross matching test: The donor's red cells are tested against

the patient’s plasma. Aiming to confirm the ABO compatibility

between, the donor & the recipient. Types:

1. Rapid cross matching is done in emergency & takes about 5-10 minutes.

2. Full cross matching takes about 20-30 minutes & can detect rare blood-group antigens present on the selected donor cells.

3. Electronic cross matching is available now & safe procedure.

BLOOD TRANSFUSION Blood grouping:

ABO antigens pre-exist on red cells & ABO antibodies pre-exist in the plasma & will cause immediate reaction if incompatible.

Blood grouping is carried out in 5 minutes by adding A,B,RhD agglutinins to donor's blood.

O Rh negative is universal donor (red cells carry no ABO/Rh antigens), it can be given safely in dire emergency if the same group is not available.

AB Rh positive is universal recipient (serum contains no A, B, RhD antibodies).

Rh factor rules: 15% of population are Rh –ve. RhD-negative patients are, as a rule,

transfused with RhD-negative red cells, but if there is a shortage of such blood, unimmunized RhD-negative men & unimmunized women above 60 years, may safely be given RhD-positive red cells.

Rh –ve females should not receive Rh +ve blood during child bearing period.

Anti-rhesus (D/E) antibodies only develop following exposure to the RhD antigen,

The RhD antigen is highly immunogenic; once anti-D is formed, it destroys RhD-positive cells → severe hemolysis in fetus/newborn. Thus it is important to type women of childbearing age, as well as girls.

BLOOD TRANSFUSION

Types of transfusion:

1. Transfusion of whole blood (fresh or banked).

2. Transfusion of bl. components.3. Transfusion of bl. substitutes

BLOOD TRANSFUSION Transfusion of whole blood:

either fresh or banked blood  

Fresh blood transfusion i.e. within 6 hours of donation. {Fresh blood is rich in blood elements that rapidly destroyed during banking e.g. platelets, coagulation factors}

Banked blood transfusion: Blood is collected in anti-coagulant

preservative (citrated phosphate dextrose solution) & stored at 40C & can be used within 28 days.

Changes in Banked blood during storage: RBCs loose their viability by time ( 2, 3 DPG

enzyme).

K (hemolysis of RBCs), Ammonia.

Platelets survival to only 1 – 2 days. Clotting factors (V & VIII) are rapidly

deteriorated.

Lactic acid & pH.

Prothrombin by ¼, after 1 W of storage.

WBCs by ½ normal values after 1 W of storage.

BLOOD TRANSFUSION Transfusion of blood

components: The only indication for whole blood

transfusion is hypovolemia due to acute hemorrhage.

  Red cell concentrates:

Prepared by centrifugation & removal of most of supernatant plasma & then, 100 ml of SAG-M, which contains sodium chloride, adenine, glucose, & mannitol are added for optimal storage of the red cells.

Shelf life of packed RBCs is 42 days. The mean volume is about 330 ml. Because the viscosity is high as there

are no plasma proteins, solution can be added to allow fast administration if necessary.

BLOOD TRANSFUSION

Special types of red cell concentrate used during organ transplantation :

Buffy coat-depleted red cell concentrates: Prepared by removal of the buffy coat of RBCs, which contains

most of the leucocytes & platelets. Removal of leucocytes prevents almost

all febrile reaction during blood transfusion .

Cytomegalovirus-seronegative red cell concentrates: Used to minimize

the risk of transmission of cytomegalovirus in bone marrow & renal

transplant recipients, & for fetal & neonatal transfusions.

BLOOD TRANSFUSION

Platelet transfusion:Prepared by plateletpheresis May be stored for up to 5 days at 22°C .Shelf life of platelets is 5 days from the

time of donation.Indicated in case of spontaneous Hge

secondary to thrombocytopenia .Before major surgery, the platelet

count must be > 100,000/µL, (50,000 for minor surgery).

During splenectomy for idiopathic thrombocytopenic purpura, Platelet

transfusion should not be administered until the splenic hilum is clamped.

Types Random donor platelet transfusion(from

many donors){risk of alloimmunization}Single donor platelet transfusion.

Six packs of random donor platelet or 1 unit of single donor platelet →↑ platelet

count by 10,000/µL.On repeated platelet transfusion, 50% of

patient show failure of platelet counts to rise by platelet transfusion

(alloimmunization) .The incidence of alloimmunization can

be decreased by using one of the followings:

Single donor platelet product .Human leukocyte antigen – matched

single donor platelet.Post-transfusion purpura: It is a rare

complication of platelet transfusion seen in multiparous women with a history of

platelet transfusion before. Clinically: at 7-10 days of transfusion, purpura, &

severe bleeding occurs (may be fatal). Management include plasmapheresis, IV

infusion of IG (platelet transfusion is ineffective & not recommended).

Side effects: transmission of infection, allergic reaction, alloimmunization &

post transfusion purpura.

BLOOD TRANSFUSION

BLOOD TRANSFUSION

BLOOD TRANSFUSION Fresh frozen plasma (FFP):

It represents the fluid portion of whole blood.

It contains all coagulation factors except platelets.

It does not need cross matching but should ABO & RhD (in females during child bearing period) compatible.

After thawing, it must be used within 20 minutes & discarded if not used for 2 hours.

It is stored at -18˚C & has a shelf life of up to 1 year.

Uses: To reverse anticoagulation (oral type)

rapidly before surgery. To correct coagulation deficiencies in liver

disease & DIC. Anti-thrombin III deficiency.

Drawback: factor V, factor VIII may be deficient (unstable during thawing process).

Dose: 10-15 ml/kg is adequate for replacement.

BLOOD TRANSFUSION

Cryoprecipitate: Prepared by allowing the frozen plasma

from a single donation to thaw at 4–8°C & removing the supernatant. The volume is about 20 ml & it is stored at —30°C.

It contains factor VII, factor VIII & fibrinogen.

It is no longer used for the treatment of hemophilia A & Von Willebrand disease because of the greater risk of virus transmission than with other available products, but it may be useful in disseminated intravascular coagulation if the fibrinogen is very low.

BLOOD TRANSFUSION

Factor VIII & IX concentrates: These are freeze-dried preparations of

specific coagulation factors prepared from large pools of plasma.

They are used to treat patients with hemophilia & von Willebrand disease.

Recombinant factor VIII is now recommended as the treatment of choice for hemophilia A because of concerns about the safety of pooled plasma products.

BLOOD TRANSFUSION

Albumin: There are two preparations:

Human albumin solution (4.5 per cent) contains 45 g/l albumin & 160 mmol/l sodium. It is produced in 50-, 100-, 250-, & 500-ml bottles.

Human albumin solution 20 per cent contains approximately 200 g/l albumin & 130 mmol/l sodium & is produced in 50- & 100-ml bottles.

Used in acute, & severe hypoalbuminemia e.g. Nephrotic syndrome, liver disease, pancreatitis.

BLOOD TRANSFUSION

Others Normal immunoglobulin: Prepared

from normal plasma. It is used in patients with hypo-gammaglobulinemia to prevent infections, & in patients with immune thrombocytopenia.

Specific immunoglobulins: Obtained from donors with high titers of antibodies. Many preparations are available, such as anti-D, antihepatitis B, antivaricella-zoster

BLOOD TRANSFUSION Blood substitutes:

 Colloids – e.g. dextran (low (40,000) or high (70,000)molecular weight dextran):As it remains in circulation for 24 hs. So, do not use more than 1½ L dextran →

To avoid hemodilution & ↓ O2 carrying capacity of blood.

To avoid overload of circulation especially in patient with respiratory or renal diseases.

Dextran causes pseudo-agglutination of RBCs, so, blood grouping & cross matching tests must be done before its administration.

Low molecular weight Dextran inhibits platelet aggregation & ↑ bleeding tendency.

Crystalloids: they are administered in 3- 4 times equal to volume of blood loss.

Future Blood Substitute (artificial blood): Polymerized Pyridoxylated

Hemoglobin: prepared by polymerization of lysed RBCs to ↓ oncotic pressure. It has been successfully used in baboons & is under clinical investigation in humans.

Synthetic Perflourocarbons & modified hemoglobin solution: They are good solvents for blood gases & can be administered immediately without cross matching. They can be stored indefinitely, but still under trial.

BLOOD TRANSFUSION

Administration of blood transfusion: During & shortly after transfusion, the

patient must be monitored closely. In adult: Transfusion of 1L blood

hematocrit by 9% & HB conc. by 1 –2 gm%.

In children: 20 cc blood / kg body weight is the recommended dose (10 cc blood / kg body weight in case of premature (better packed RBCs).

BLOOD TRANSFUSIONComplications of blood

transfusion:Hemolytic reaction:

Cause: Incompatible blood transfusion. Antibodies are formed against transfused RBCs.

Time: Most reactions occur during early period of transfusion but it should be observed during the whole transfusion.

Clinical features :At the site of injection severe burning pain

at the site of injection.Chest & heart tight chest pain &

breathlessness & hypotension & tachycardia.

General fever chills, flushing.Patients under anesthesia – show the

following changes Unexplained oozing of blood .

Change in vital signs (hypotension & tachycardia).

Later on hemoglobinuria.

BLOOD TRANSFUSION

Treatment: Stop transfusion & samples of transfused

& patient’s blood are taken for analysis. Forced diuresis to keep urine output at

100 ml/minute. (Diuretics & mannitol). NaHCO3 to correct acidosis & -ve renal

damage as it helps to prevent precipitation of Hb in renal tubules (2 ampoules of 7.5 Na bicarbonates /1 L D5W)

Corticosteroids, vasopressor, & O2.

BLOOD TRANSFUSION

N.B: Delayed extra vascular hemolytic transfusion reactions: It occurs 7-10 days after transfusion. It is an antibody mediated reaction.

Because the antibody titer was too low to be detected by pre transfusion compatibility tests, it delays till secondary antibody response occurs by IgG → accelerated destruction of transfused RBCs → anemia, jaundice & fall of hematocrit.

As hemolysis is extravascular, hemoglobinemia & hemoglobinuria are uncommon.

BLOOD TRANSFUSION

Non hemolytic transfusion reaction: Allergic reaction:

Cause: Allergens in donor’s blood. Clinically Mild reaction in the form of

skin rashes & itching (treated by anti-histaminics) or severe in the form of laryngeal edema & anaphylaxis (treated by corticosteroids).

Febrile reaction:

Cause: Pyrogens on donor’s leucocytes & platelets.

Treatment: Antipyretics, exclude hemolytic reaction (stop transfusion & send samples for analysis).

BLOOD TRANSFUSION

Transmission of infection: Viral: (Viral hepatitis – especially none A

non B type, AIDS), human T cell lymphoma virus, cytomegalovirus, West Nile virus & others. Immunosuppressive patient must receive cytomegalovirus seronegative red cells.

Bacterial e.g. brucella, staph, enterobacter, pseudomonas, Yersinia. The conditions is characterized by hyperpyrexia & hypotension & treated by volume expansion, blood culture & broad spectrum antibiotics.

Protozoal e.g. malaria, Spirochetal e.g. syphilis.

BLOOD TRANSFUSION Complications of massive

transfusion of banked blood: Definition: Rapid transfusion of amount

of banked blood equals or exceeds the patient’s blood volume.

Effects: Metabolic Effects: K, PH, Ca, citrate

toxicity. Hypothermia {when several units are

transfused without being warmed}. Respiratory insufficiency; Micro circulatory

blockage by minute thrombi in old blood. The incidence of this complication has been greatly reduced after transfusion of blood through 40 micron mesh filter.

Hemorrhagic diathesis as result of platelet & coagulation factors deficiency.

BLOOD TRANSFUSION

N.B: Transfusion-related acute lung injury: Cause: antibody mediated reaction

against donor HLA typically within 6h of transfusion. .

Activated recipient leucocytes release proteolytic enzymes at the lung → capillary leak syndrome & non-cardiogenic pulmonary edema,

BLOOD TRANSFUSION

Autologous blood transfusion :The use of patient’s own blood for the

replacement of blood lost during surgery .

Types:Preoperative – either →

Preoperative hemodilution: One or two units of blood are removed from the patient

immediately before surgery & retransfused to replace operative losses. During surgery, the blood is diluted & there is no much loss

of blood.Pre deposit Blood Transfusion: i.e. elective

donation of multiple units in weeks before surgery 2-5 units & the patients is

maintained on oral ferrous sulphate . 

Per-operative blood salvage:The blood loss at the operative field is

collected by special suction system & re-infused after washing & suspension in

normal saline.Advantage: The method is of great value in

vascular surgery e.g. average units of banked blood required during surgery for

aortic aneurysm are decreased from 4 units to zero.

LOCAL HEMOSTATIC AGENTS

Type Use Side effects

Gelatin sponge Provide a plateform For coagulation, but it is not intrinsically hemostatic.

Oxidized cellulose surgicel

Knitted fabric of cellulose that allows clotting by absorbing the blood.

Foreign body reaction

Collagen sponge helistat

Promote platelet adhesion. From bovine tendon.

Foreign body reaction

Micro-fibrillar collagen hemotene

Sprayed into the wound in areas difficult to reach. It stimulate platelet adhesion & clot formation

Topical thrombin

As lyophilized powder or dissolved in saline & sprayed into wound. Achieve fibrin rich fibrin plug. Used with hemostatic agents or to the dressing at the bleeding sites.

Gelatin matrices floseal

With topical thrombin intraoperatively to control bleeding site.

THANK YOU