The micrograph shows activated platelets adhering to some damaged

cells

Hemostasis

Content

• Defination• Normal vessel wall• Stages of haemostasis• Anti clotting mechanism• Applied

Defination

• Term haemostasis means prevention of blood flow.

• It is a process of forming clots in the walls of damaged blood vessels and preventing blood loss while maintaining blood in a fluid state within the vascular system.

• Normal hemostasis is a consequence of tightly regulated process that maintain blood in a fluid state in normal vessels, yet also permit the rapid formation of a hemostasis clot at the site of a vascular injury.

HEMOSTASIS

6

HEMOSTASISThe process of hemostasis can be divided into two distinct stages namely:1. Primary hemostasis – platelet plug formation2. Secondary hemostasis – coagulation cascade

• The goal of both primary and secondary hemostasis is to arrest bleeding from damaged blood vessels (hemo = blood, stasis = standing)

• Is counter-balanced by reactions, which prevent blood coagulation in uninjured vessels and maintain the blood in a fluid state– Balance between procoagulants and anticoagulants

• 4 overlapping processes or stages– Local vasoconstriction– Formation of a platelet plug– Formation of a web of fibrin proteins that penetrate and surround the platelet plug –

blood coagulation or clotting – Clot retraction.

7

LOCAL VASOCONSTRICTION• Results from

– Release of vasoconstrictor substances (paracrine & autocrine agents) from

• Platelets (i.e., serotonin & thromboxane A2) • Traumatized tissue

– Local myogenic spasm initiated by direct tissue damage– Reflex vasoconstriction initiated by activation of nociceptors and

other sensory endings

• Effects– ↓ blood flow and Pressure in the damaged area

Last for many minutes or even hours, during this time the ensuing processes of platelet plugging and blood

coagulation can take place

FORMATION OF A PLATELET PLUG (temporary hemostatic plug, white plug)

Intact blood vessel wall

Adhesion of the platelets

Platelet release reaction & activation

Platelet aggregation & plug retraction

Secretion of prostacyclin & nitric oxide

Local vasoconstriction

Collagen fibers are exposed to the blood and coated with WF*

Damaged blood vessel wall

-

-

-

Temporary hemostatic (platelet) plug

Factors that prevent/limit formation of a plug

1. Prostacyclin (prostaglandin I2).Inhibits platelet aggregation; vasodilator

2. Nitric oxide* (NO).Inhibits platelet adhesion, activation and aggregation and stimulates local vasodilation

* Von Willebrand factor, a protein synthesized by endothelialcells and megakaryocytes, enhances platelet adherence by forming a bridge between cell surface receptors and collagen in the subendothelial matrix.

+ stimulation- inhibition

+

+

9

FORMATION OF A PLATELET PLUG (cont.)Stage 1. Platelets adhesion

vWF binds to glucoprotein Ib receptors of platelets and to collagen

Failure of this step may be due to:- Absence of von Willebrand factor - Malfunction of collagen -

A. vWF - von Willebrand factor (soluble plasma protein) binds to collagen of subendothelial matrix

B. vWF exposes multiple intrinsic binding sites for the platelet specific membrane glycoprotein Ib (GPIb)

Scurvy

10

FORMATION OF A PLATELET PLUG (cont.)Stage 2-3 Platelets release reaction and activation. Binding of the platelets to the collagen → Release of agents from secretory granules (degranulation) – serotonin, adrenaline, several clotting factors, thromboxane A2, tissue factor and ADP Serotonin, adrenaline and ADP act locally → changes in the metabolism, shape, and surface proteins of the platelets.

Serotonin and thromboxane A2 stimulate local vasoconstriction

Primary Hemostatsis

Subendothelium

Endothelium

Von willebrand factor

GpIb

Deficiency: Glanzmann thombasthenia

GpIIb-IIIa complex

Fibrinogen

Platelet

Step 1: Transient vasoconstriction (endothelin)

Step 2: Platelet adhesion - von

willebrand factor bind to the disrupted blood vessel via GpIb

Step 3: Platelet release ADP and thromboxane A2 which stimulate adhesion of the next layers of platelets (recruitment) through a positive feedback mechanism and formation of a platelet plug inside the vessel ADP induces platelet to express GpIIB-IIIa which is needed to platelets aggregation via fibrinogen

Step 4: Platelet aggregation (Platelt plug)

GpIb

Deficiency: Bernard-Soulier syndrome

12

FORMATION OF A PLATELET PLUG (cont.)

• ADP and thromboxane A2 stimulate adhesion of the next layers of platelets (recruitment) through a positive feedback mechanism and formation of a platelet plug inside the vessel

Failure of this step:- Insufficient number of platelets - Dysfunctional platelets (prior activation

occurs during cardiopulmonary bypass, storage, exposure to aspirin, uraemia and acute and chronic alcohol exposure)

Stage 4: Recruitment and loose platelets aggregation

GpIIb-IIIa complex

Platelet

12

Normal Blood Vessel

Injured blood vessel

Exposed collagen binds and activates

platelets

Release of Platelet factors

Attracts more platelets

Aggregate into platelet plug

Secondary Hemostasis

This involve the conversion of the fibrinogen (solube) in the platelet plug to fibrin (insoluble).Fibrin is then cross-linked to yield a stable platelet-fibrin thrombus.

Secondary hemostasis involve the activation of coagulation cascade factors in both intrinsic and extrinsic pathways

17

BLOOD COAGULATION (CLOTTING)• Is the transformation of the blood into a solid gel (a clot or thrombus)• Occurs locally around the platelet plug; supports and reinforces the

plug• Requires 12 plasma clotting factors and platelets • Involves a cascade of biochemical reactions in which each factor that

is activated in turn activates the next factor • The fundamental reaction is conversion a soluble protein, fibrinogen

to an insoluble protein, fibrin

In coagulation a series of plasma proteins called blood-clotting factors play major roles.

Most of these are inactive forms of proteolytic enzymes. When converted to the active forms, their enzymatic actions cause the successive,

cascading reactions of the clotting process.

Coagulation System

Consists of a cascading system of proteins– Primarily originating from liver (except factor III)– Circulate in inactive form – System includes:

• Enzymatic factors• Non-enzymatic factors• Tissue thromboplastin (factor III)• Calcium (factor IV)• Platelet phospholipid (PF 3) - structural component; accelerates factor

activation• Anticoagulant factors

The coagulation system consists of three pathways (intrinsic, extrinsic and common)

Scientific Name Common Name Main Function

Factor I Fibrinogen Converted to fibrin

Factor II Prothrombin Enzyme

Factor III Tissue thromboplasm Cofactor

Factor IV Calcium Cofactor

Factor V Proaccelerin Cofactor

Factor VII Proconvertin Enzyme

Factor VIII Antihemophilic factor Cofactor

Factor IX Christmas factor Enzyme

Factor X Stuart factor Enzyme

Factor XI Plasma thromboplatin antecedent Enzyme

Factor XII Hageman factor Enzyme

Factor XIII Fibrin stabilizing factor Enzyme

PLASMA CLOTTING FACTORS

20

3 PHASES OF BLOOD COAGULATION• Formation of a complex of activated substances - prothrombinase

(prothrombin activator)

• Formation of active thrombin from prothrombin– Is catalyzed by prothrombin activator

• Formation of insoluble fibrin from soluble fibrinogen– Is catalyzed by thrombin

PHASE 1 – FORMATION OF PROTHROMBINASE

XII

XI

II

XIa

XIIIa

XIII

IX

X

XIIa

Ca2+IXa

PF-3Ca2+VIII Xa

PF-3Ca2+

VX

Thrombin

Fibrinogen Fibrin Stable fibrin polymer

INTRINSIC PATHWAY EXTRINSIC PATHWAY

IIICa2+

VIIa VII

22

PHASE 3 – FORMATION OF FIBRIN• Thrombin catalyses release of 2

pairs of polypeptides from each fibrinogen molecule and formation of fibrin monomers– Ca++ and platelet factors are

also required

• Monomers join together to form insoluble fibrin polymers – a loose mesh of stands

• Stabilization of fibrin – formation of covalent cross-bridges, which is catalyzed by factor XIII (+ Ca++)

23

FINAL EVENTS OF HEMOSTASIS• Fibrin forms a meshwork, which supports

the platelet plug

• Clot occludes the damaged blood vessel and ↓ or stops bleeding

• Retraction of the clot due to contraction of fibrin fibers and contractile proteins of the platelets – ↑ clot density– Occlusion of the damaged vessel– Bringing the edges of wound together

→ facilitation of wound heeling

• Fate of the blood clot– Invasion by fibroblasts → formation of

connective tissue through the clot– Fibrinolysis and destruction of the clot

Dissolving the Clot

Figure 16-14: Coagulation and fibrinolysis

Clot Dissolution• Plasmin (fibrin-digesting enzyme) is made from activating

plasminogen (blood protein)– Presence of the clot causes endothelial cells to release

tissue plasminogen activator– Fibrinolysis begins within 2 days and continues slowly over

several days until the clot is dissolved.ra

Plasminogen Plasmin

Activator (e.g. t-PA)

Fibrin soluble fragments

26

Fibrinolysis Clinical application-

Human t-PA is produced by recombinant DNA technology and available for clinical use. lyses clots in the coronary arteries if given to

patients soon after the onset of myocardial infarction.

Streptokinase (from bacteria-streptococcci) and urokinase are also fibrinolytic enzymes used in the treatment of early myocardial infarction

Clot retraction & repair

• Clot retraction occurs within 30-60 minutes.• Platelets contain actin & myosin • As clot is compacted fibroblasts (stimulated by platelet-

derived growth factor -PDGF) rebuild the wall while endothelial cells (stimulated by vascular endothelial growth factor -VEGF) multiply to restore the lining

Overview of Hemostasis and Tissue RepairDamage to

wall of blood vessel

Vasoconstriction

Temporary hemostasis

Collagen exposed

Platelets aggregate into loose platelet plug

Intact blood vessel wall

Cell growth and tissue repair

Clot dissolves

Fibrin slowly dissolved by plasmin

Thrombin formation

Tissue factor exposed

Coagulation cascade

Converts fibrinogen to

fibrin

Platelets adhere and release

platelet factors

Reinforced platelet plug (clot)

30

ROLE OF VITAMIN K IN CLOTTING • Vitamin K acts as a cofactor of the enzyme γ-glutamyl carboxylase

• Is required for γ carboxylation in the liver of – Prothrombin and factors VII, IX and X – Proteins S and C (natural anticoagulants)

Vit K is activated by epoxide reductase in the liver

• γ carboxylation (introduction of a carboxylic acid group) of certain glutamate residues in target clotting factors → binding sites for Ca++ and PF3

• most of clotting factors are synthesized by the liver. Therefore, liver diseases (i.e., hepatitis, cirrhoses, atrophy) depress the clotting system. Decreased dietary intake of vit K has limited consequences on blood clotting because Vit K is continuously synthesized by the intestinal flora. Note that Vit K is fat soluble and requires fats for absorption. Lack of the bile decreases fat digestion and absorption.

31

ROLE OF Ca++ IN COAGULATION

• Ca++ is required for all steps of coagulation (except first 2 steps of the intrinsic pathway)

• ↓ in the plasma [Ca++] below the threshold level for clotting → ↓ blood clotting by both pathways

32

ROLE OF THE PLATELETS IN COAGULATION

Activated platelets

• Display specific plasma membrane receptors that bind several of the clotting factors → several cascade reactions take place on the surface of activated platelets

• Display phospholipids (platelet factors), which act as cofactors of the bound clotting factors

33

ROLE OF THE LIVER IN BLOOD COAGULATION

• Synthesis of the plasma clotting factors

• Synthesis of the bile salts, which are required for intestinal absorption of lipid soluble vitamin K

Anti clotting mechanism

Anti clotting mechanism

1. Smoothness of endothelium (glycocalyx)2. Thrombomodulin3. Fibrin fibers and anti thrombin III4. Heparin5. Plasmin6. Prostacyclin7. 2 macroglobulin

8. Circulating blood

• Antithrombin III – inhibits factor X and thrombin

• Fibrin acts as an anticoagulant by binding thrombin and preventing its:

• Heparin – a natural anticoagulant,potentiates effects of antithrombin III (together they inhibit IX, X, XI, XII and thrombin

• Antithromboplastin (inhibits „tissue factors” – tissue thromboplastins)

• Protein C and S – degrade factor Va and VIIIa

37

NATURAL ANTICOAGULANTS (cont.)

Endothelial cell

Thrombomodulin

Thrombin

Protein C

Activated Prot C

Protein S

Inactivation of inhibitors of plasminogen activator

Plasminogen

Fibrinolysis

Thrombin/thrombo-modulin/protein C pathway

Thrombomodulin is a thrombin-binding endothelial cell receptor

Binds thrombin and inactivates it

Complex of thrombin+thrombo-modulin binds protein C and activates it

Protein C in collaboration with protein S inactivates factors Va and VIIIa and activates plasminogen and fibrinolysis

VVaVIIIViIIa

Plasmin

Thrombin

Note: Mutated factor V cannot be inactivated (switched off) by activated protein C, and this will lead to hypercoagulable state

38

DRUGS THAT INHIBIT BLOOD CLOTTING (ANTICOAGULANTS)

• Heparin: Heparin binds to the enzyme inhibitor antithrombin III (AT), causing a conformational change that results in its activation. The activated AT then inactivates thrombin and other proteases involved in blood clotting such as XIIa, XIa, Xa and IXa

• Coumarin derivatives (i.e., warfarin) – Block stimulatory effects of vitamin K on synthesis of clotting

factors II, VII, IX, and X by the liver (inhibit epoxide reductase which activates vit K in the liver: K → K1)

• Aspirin – Low doses inhibit prostaglandins and thromboxanes synthesis by

the platelets → inhibition of platelet release reaction and platelet aggregation

– Is effective in preventing of heart attack and reduction of the incidence of sudden death

39

IN VITRO INHIBITION OF BLOOD CLOTTING• Keeping of blood in seliconized containers – prevention of contact activation of

platelets and factor XII

• Substances that bind ionized calcium to produce un-ionized calcium compound or to form insoluble salts with calcium – Sodium citrate or oxalate– Ammonium or potassium citrate– EDTA (ethylenediaminetetraacetic acid)

• Is ability to "sequester" di- and tricationic ions (Ca2+ & Fe3+)• Is widely used as an anticoagulant for blood samples for complete blood

count/full blood examination

• Heparin

Bleeding time This is a test that measures

the speed in which small blood vessels close off (the condition of the blood vessels and platelet function)

This test is useful for detecting bleeding tendencies

The bleeding stops within 1 to 4 minutes. This may vary from lab to lab, depending on how the test is measured

Whole blood clotting time

The time taken for blood to clot mainly reflects the time required for the generation of thrombin

The surface of the glass tube initiates the clotting process. This test is sensitive to the factors involved in the intrinsic pathway

The expected range for clotting time is 4-10 mins.

Tests of coagulation

"Intrinsic" and "extrinsic" coagulation pathways

N: 9.9 – 13 secActivated Partial Thromboplastin Time

N: 25-35 sec

Prothrombin Time

44

PROTHROMBIN TIME (protime, PT test)• Measures the clotting time of

plasma from the activation of factor VII, through the formation of fibrin clot

• Assesses the integrity of the extrinsic/tissue factor pathway and common pathways of coagulation (factors VII, X, V, II, I)

• The PT test is widely used to monitor patients taking anticoagulants as well as to help diagnose clotting disorders

Diagnostica Stago training, 2005 45

Prothrombin Time

Thromboplastinand Calcium

Patient’s Plasma

Factors

IIIVVIIX

Prothrombin time (PT) test – norm 11 -15 secevaluates extrinsic system (VII, X, V, II, fibrinogen)

• prolonged PT indicates a deficiency in any of factors VII, X, V, prothrombin (factor II), or fibrinogen (factor I).

• Prolonged PT:-   a vitamin K deficiency (vitamin K is a

co-factor in the synthesis of functional factors II (prothrombin), VII, IX and X)

-    liver disease Warfarin therapy DIC excesive heparin

47

PROTHROMBIN TIME (cont.)• Depends on [prothrombin] in the blood

• Normal range 12 – 14 sec

• Increased– ↓ prothrombin (less than 10% of normal)– Deficiency of fibrinogen or factors V, VII, or X – Therapeutic anticoagulants (i.e., heparin,

warfarin, aspirin), some drugs (i.e., antibiotics, anabolic steroids, estrogens, etc.)

– Liver diseases– Vit K deficiency – Disseminated intravascular coagulation

• Decreased– Vit K supplementation– Thrombophlebitis

48

ACTIVATED PARTIAL THROMBOPLASTIN TIME

(aPTT) • Assesses the integrity of the intrinsic and common pathways

of coagulation

• Measures the clotting time of plasma, from the activation of factor XII by a reagent through the formation of fibrin clot

• Normal range 25 – 38 sec

• Prolonged time– Use of heparin– Antiphospholipids antibodies– Coagulation factors deficiency (intrinsic and common pathways; i.e.,

hemophilias)

Diagnostica Stago training, 2005 49

Activated PartialThromboplastin Time

Ca++

Patient’s Plasma

FactorsIIIVVIIIIXXXIXII

Phospholipidand Activator

Activated Partial Thromboplastin Time test (aPTT) – norm: 25-35 s; evaluates intrinsic system (VIII, IX, XI, XII, X, V, II,

fibrinogen) • an isolated prolongation of

the aPTT (PT normal) suggests deficiency of factor VIII, IX, XI or XII

• prolongation of both the APTT and PT suggests factor X, V, II or I (fibrinogen) deficiency, all of which are rare

• aPTT is normal in factor VII deficiency (PT prolonged) and factor XIII deficiency

Most common case of prolonged aPTT – heparin!!!

Diagnostica Stago training, 2005 52

Thrombin Clotting Time

Low concentrationof thrombin

Undiluted patient’splasma

Screens foreffects of • Heparin • FDPs

Thrombin time (TT) – norm: 14-15 sec

Prolonged TT:• Heparin (much more sensitive to heparin

than aPTT)• Hypofibrinogenemia

Selected causes of abnormal coagulation tests

Partial Thromboplastin

Time (aPTT)

Prothrombin Time (PT)

Thrombin Time (TT)

Bleeding Time (BT)

Factor deficiency (except VII)

VII, X, V, II, fibrinogen deficiency

Low or absent fibrinogen

Thrombocytopenia

Antibodies to clotting factors

Antibodies Dysfibrinogenemia, hypofibrinogenemia

Von Willebrand’s disease

Heparin Warfarin; Vit K defficiency (mild to severe)

Heparin Drugs (Aspirin, NSAIDs, high dose penicillins, etc.)

Excessive Warfarin Excessive Heparin Cirrhosis, Uremia, PLTs dysfunction

56

2 TYPES OF ABNORMALITIES OF HEMOSTASIS

• Excessive bleeding (hemorrhagic disease) caused by deficiency of a clotting factor/s or platelets

• Excessive clotting: thrombosis, embolism, disseminated intravascular coagulation

57

CONDITIONS THAT CAUSE EXCESSIVE BLEEDING

• Vitamin K deficiency

• Deficiency of clotting factors (i.e., hemophilia)

• Deficiency of thrombocytes – thrombocytopenia

• Deficiency of von Willebrand factor

58

VITAMIN K DEFICIENCY• Results from

– ↓ intestinal absorption of fats due to ↓ bile secretion (i.e., liver disease or obstruction of the bile ducts)

– ↓ dietary intake of vit K (limited importance)

• Results in – ↓ hepatic gamma carboxylation of

• Prothrombin (II)• Factors VII, IX and X• Protein C and S

– Bleeding tendency• Prolonged prothrombin time and partial thromboplastin time• Normal platelets count and serum fibrinogen split products

59

HEMOPHILIA

• Is a hemorrhagic disease that results from deficiency of – Factor VIII (the smaller component) - hemophilia A

or classical – Factor IX – hemophilia B, Christmas disease – Factor XI – hemophilia C

• Is a genetic disease– Hemophilia A and B are sex linked (X chromosome)

• Occur in males• Females are hemophilia carriers

• Results in ↑ aPTT (PT, thrombocytes count, fibrin split products are normal)

Hemophilia A (lack of F VIII; 85%)

• Spontaneous or traumatic subcutaneous bleeding

• Blood in the urine• Bleeding in the mouth,

lips, tongue• Bleeding to the joints,

CNS, gastrointestinal tract

Mild hemophilia after injection in buttock

Deficiency Factor

Clinical Syndrome Cause

Factor I Afibrinogenemia Depletion during pregnancy with premature separation of placenta: Congenital

Factor II Hypoprothrombinemia (Hemorrhagic tendency in liver diseases

Decreased hepatic synthesis (secondary to vitamin K deficiency)

Factor V Parahemophila Congenital

Factor VII Hypoconvertinemia Congenital

Factor VIII

Hemophilia A (classical hemophilia)

Congenital recessive sex-linked defect due to abnormalities of the gene that codes for factor VIII (X chromosome)

Factor IX Hemophilia B (Christmas disease)

Congenital recessive trait carried on X chromosome

Factor X Stuart-Prower factor deficiency

Congenital

Hemophilia C (PTA deficiency

Congenital

Hageman trait Congenital

HEMOPHILIA

62

THROMBOCYTOPENIA• Low thrombocytes count (below 50 000/m l) → poor plug formation,

deficient clot retraction, deficient platelet phospholipids, poor constriction of ruptured vessels → bleeding tendency from many small venules and capillaries

• Multiple hemorrhages in the skin and mucous membranes – thrombocytopenic purpura– Petechiae – small punctate hemorrhages(1-3 mm)– Echymoses - large hemorrhages (bruises)

• Other causes of purpura– ↓ plasma level of 1 or more clotting factors– ↑ fragility of capillary walls (congenital, Vit C deficiency,

adrenal failure, toxins, drugs, allergic reactions)

Thrombocytopenia Severe reduction in the

number of PLTs - thrombocytopenia

this causes spontaneous bleeding as a reaction to minor trauma

in the skin - reddish-purple blotchy rash

it may result from: decreased production (toxins, radiation,

infection, leukemias) increased destruction (autoimmune

processes) increased PLTs consumption (DIC)

Hemorrhagic spots (petechiae)

64

von Willebrand’s disease

• Is the most common genetic bleeding disorder

• Results from defect in vWF ( quantitative or functional)

• Results in combination of– Platelet function abnormality (vWF) - impaired adhesion– Clotting factor deficiency (factor VIII) - ↑ aPTT (PT is normal)

65

THROMBO-EMBOLIC CONDITIONS• Thrombosis - blood clotting within the CVS which obstruct the blood flow through

the CVS (Should be distinguished from extravascular clotting, clotting in wounds and clotting that occurs in the CVS after death). Thrombosis is rather a pathological condition.

• Common causes– Roughened endothelial surface (i.e., atherosclerosis, infections, traumas)– Slow blood flow– Hypercoagulobility– Acquired refers to transient or acquired conditions that increase the tendency

to clot. This might include antiphospholipid antibodies or a temporary hypercoagulable state such as pregnancy. Also, advanced carcinomas of the pancreas or lung may produce a hypercoagulable state.

– Congenital refers to hereditary conditions that increase the tendency to clot. These include Factor V Leiden, prothrombin ,protein C, protein S and antithrombin deficiencies

ConsequencesFormation of emboli (thromboembolism) – braking down of the thrombus and spreading of its particles particles throughout the CVS

Thrombosis in the left side of the heart and large arteries → emboli in the brain, kidneys, etcThrombosis in the venous system and in the right side of the heart → emboli in the pulmonary circulation

Disseminated intravascular coagulation (DIC)

• Widespread coagulation thrombosis in small blood vessels increased fibrinolysis, and depletion of coagulating factors generalized bleeding

• It may result from:- bacterial infections

(endothelial damage)- disseminated cancers

(release of procoagulants)- complications of pregnancy- severe catabolic states Disseminated cervical

cancer metastases (PET imaging)

68

DESSIMINATED INTRAVASCULAR COAGULATION

• Reasons– Large areas of necrotic tissue (release of tissue factors into the blood)– Septicemia (activation of clotting by circulation bacteria and bacterial

toxins)

• Consequences– Consumption coagulopathy

• ↓ fibrinogen, thrombocytopenia• ↑ fibrin split products• ↑ PT and PTT

69

CHALENGE YOURSELF 1/5A baby is born prematurely at 28 weeks gestational age with a birth weight of 1200 g. A few weeks after birth his mother noticed a bleeding tendency in the infant. Blood test revealed a low prothrombin level. Which vitamin can be given to the baby to reduce or to prevent the bleeding tendency?a. Vitamin B12b. Vitamin B6c. Vitamin Kd. Folic acid e. Vitamin A

Answer is C

CHALENGE YOURSELF 2/5

• A 72-year-old African-American man undergoes hip surgery. On his third hospital day he experiences chest pain, tachycardia, dyspnea, and a low-grade fever. The man goes into cardiac arrest, and efforts to resuscitate him are unsuccessful. On autopsy a massive pulmonary embolus is discovered. Which of the following, if present, would most likely predispose the patient to this event?

(A) Factor VIII defi ciency(B) Low serum homocysteine levels(C) Mutation in the Factor V gene(D) Overproduction of protein C(E) von Willebrand factor defi ciency

Answer is C

CHALENGE YOURSELF 3/5

Taking aspirin every day can reduce the risk of heart disease becausea.it is a powerful vasodilator b it stimulates fibrinolysis c. it prevents atherosclerosis d.it loosens atherosclerotic plaque on arterial walls e. it prevents platelet aggregation

Answer is E

CHALENGE YOURSELF 5/5

• A 65-year-old man presented with history of acute chest pain that radiates to his left arm. Coronary angiography demonstrates more than 75% occlusion of his coronary artery. He was administered a thrombolytic agent for reestablishment of blood flow to the dying myocardium. The thrombolytic agent activates:

A. HeparinB. ThrobinC. Plasminogen D. KininogenE. Prothrombin

The Answer is C

Fill in the gap please

PT PTT Platelet Count

Bleeding Time

Reticulocyte

Megakyryocyte

D-Dimer Schicocyte

Hemophilia A N N N N N No No

Hemophilia B

vWF disease

Vit K Def

Liver Disease