Disorders of Haemostasis

Question 1

Haemostasis

Answer 1

The immediate arrest of haemorrhage depends on
Vasoconstriction
Adhesion
Aggregation
Leading to the platelet plug
Then the activation of the coagulation system
Formation of the fibrin clot

Question 2

Endothelium

Answer 2

Healthy endothelium expresses ecto-ADPase (CD39) and produces prostacyclin (PGI2) and nitric oxide (NO)
All these block platelet adhesion to and activation by healthy endothelium.
Also has active anticoagulant mechanisms

Question 3

Primary Haemostasis Platelet Disorders

Answer 3

Platelet disorders
Quantitative – thrombocytopenia or thrombocytosis.
Qualitative – functional defect can be inherited or acquired.
Acquired - drugs, alcohol, uremia and myeloproliferative disorders

Question 4

Thrombocytopenia

Answer 4

Normal platelet count 150-350 x109/L
<150x109/L
Mild (50-150), moderate (20-50) or severe(<20)
Bleeding seldom occurs >50x109/L.
Minor >10x109/L.
Spontaneous <10x109/L.
Clinical bleeding doesn’t always correlate with plt count due to other factors e.g. endothelium integrity and platelet functionality.

Remember the Causes

P- Platelet disorders
L- Leukaemia
A- Anemia
T- Trauma
E- Enlarged Spleen
L- Liver Disease
E- Ethanol
T- Toxins
S- sepsis

Question 5

Diagnosing Thrombocytopenia

Answer 5

Full blood count.
Blood film. Number, size, colour of platelets.
Platelet clumping – citrate sample.
Large platelets – congenital thrombocytopenias e.g. BS or MH or ^ turnover e.g. ITP or consumption syndromes.
Small platelets – Wiskott-Aldrich
Red cell fragments – thrombotic microangiopathy.
Hypogranular neutrophils – myelodysplasia.

Question 6

Thrombocytopenia Etiology

Answer 6

Exclude congenital thrombocytopenia’s - previous normal count.
Exposure to drugs e.g. Alcohol or quinine.
Viral infections e.g. HIV or CMV.
Post operative – dilutional – will resolve, cardiac surgery – may persist.
autoimmune – ITP, Anti-phospholipid syndrome and post transfusion purpura.

Question 7

Immune thrombocytopenic purpura (ITP

Answer 7

Incidence 2.5/100,000 in >60yrs 4.5/100,000.
Petechial rash or oral bleeding.
Platelets >50 – no treatment necessary.
Children ITP usually acute, self limiting
Adults thrombocytopenia may be prolonged
<30 or bleeding - prednisone given
<20 – hospitalised.
Anti-D, IgG, Rituximab, cyclophosphamide splenectomy.

Question 8

Thrombotic microangiopathies.

Answer 8

Endothelial injury which can result in thrombosis in cap and art.

Include TTP, HUS, HELLP(Haemolytic anaemia with Elevated Liver enzymes and Low Platelet count) and HIT.
Ischaemic injury to one or more organ or tissue.
Red cell fragments, reticulocytosis, thrombocytopenia and raised LDH.

Question 9

Thrombotic microangiopathies. Treatment

Answer 9

TTP – plasma exchange (ADAMTS13)
HUS – withdrawal of drugs
HELLP- delivery of fetus and placenta
HIT – cessation of heparin and administration of antithrombotic agents.

Question 10

Platelet function defects.

Answer 10

Bernard Soulier GP 1b-IX-V.
Thrombocytopenia, large platelets, impaired binding of VWF.
Poor platelet adhesion and aggregation.
Glanzmann thrombasthenia. GP IIb/IIIa.
Fails to bind fibrinogen.
Platelet count is normal but no aggregation with agonists e.g. ADP, epinephrine and collagen.

Question 11

Platelet transfusions.

Answer 11

Contraindicated in TTP and HIT
Limited indications
Transmit infections
Sensitise recipient to platelet antigens – HLA matched platelets necessary.

Question 12

Secondary Haemostasis

Answer 12

End of coagulation cascade is a fibrin clot.
Extrinsic. Intrinsic. Common pathway
Fibrinolysis occurs generating plasmin which dissolves the clot. The fibrinogen split products generated prevent further clotting by inhibiting fibrin polymerisation and platelet aggregation.

Question 13

Extrinsic pathway.

Answer 13

Main pathway for initiation of coagulation is extrinsic pathway
Exposure of TF binds to factor VII activating factor X. The prothrombinase complex (FX,FV, calcium and plt phospholipid activates prothrombin to thrombin ( a small amt) which then activates FXI leading to INTRINSIC

Question 14

Intrinsic Pathway

Answer 14

The intrinsic pathway amplifying the coagulation cascade
FIXa, FVIII, calcium and phospholipid (tenase complex) amplify the activation of FX generating large amts of thrombin.
Thrombin cleaves fibrinogen to form soluble fibrin monomers which polymerise to form soluble fibrin polymer.
Thrombin then activates FXIII which with calcium cross links and stabilises the fibrin polymer forming cross linked (insoluble) fibrin.

Question 15

Positive Feedback

Answer 15

Thrombin activates FXI on the platelet surface which can activate FIX to enhance FXa generation.
High levels of thrombin can cleave PAR4 – plt shape change – Stabilisation of platelet plug.
High levels of thrombin generated at propagation phase bind to fibrin and are protected from inhibition by antithrombin.

Question 16

Localisation

Answer 16

Thrombin released from the platelet plug is swept downstream- antithrombin – half life of thrombin <1 minute.
FXa is rapidly inhibited by TFPI.
Thrombin on healthy endothelial cells participate in a negative feedback loop. Thrombin binds to thrombomodulin causing a conformational change – no longer cleave fibrinogen.
This is rapidly inhibited by protein C inhibitor. Rapidly dissociates so thrombomodulin can bind thrombin and activate protein C. Activated protein C and S inactivate factor Va and FVIIIa. This confines thrombin generation to site of injury in healthy endothelium.

Question 17

Deficiencies of protein C and S

Answer 17

Deficiencies of protein C and S or defects that prevent cleavage and inactivation of FV (FV Leiden) allow for the spread of thrombi into the vasculature and are associated with venous thrombisis.

Question 18

Fibrinolysis

Answer 18

Plasminogen is central enzyme.
Activators are tissue plasminogen activator (t-PA) and urokinase (u-PA).
Plasmin cleaves the fibrin network and releases FDP (D and E). Also cleaves fibrinogen – fragment X and Y, can impair plt aggregation and fibrin polymerisation.
u-PA precursor is mediated by FXIIa, kallikrein and by plasmin.

Question 19

Fibrinolysis defects.

Answer 19

Hyperfibrinolysis – disposes to bleeding and thrombosis.

Hypofibrinolysis – deficiencies of t-PA or u-PA, plasminogen, contact factors. Associated with thromboembolic disease.

Question 20

FACTORS 1-4

Answer 20

GRID!

Question 21

Factor VIII.

Answer 21

Haemophilia A.
1 in 10,000 affected.
X-linked.
Most common mutation (up to 50%) in severe Haem A is a major inversion in Intron 22.
Severe <1% - recurrent spontaneous bleeding.
Moderate 1-5% -may be spontaneous bleeding, bleeding after trauma and surgery.
Mild 5-50% - bleeding after trauma or surgery but no spontaneous bleeding.

Severe - 6-9months (earlier if intramuscular injection received).
Mild /moderate usually present later dependant on levels.
Common sites - joints, muscles, brain.
Repeated hemarthroses leads to joint destruction. Compartment syndrome leading to necrosis and muscle shortening.

Treat until bleeding stops
Factor VIII Concentrates – Beriate.
Recombinant Prophylaxis – Recombinate, Refacto. Thrice weekly.
Complication is the development of inhibitors (10-15%).
New extended half -life factor concentrates – Elocta, Novo8
Hemlibra is a novel antibody that mimics FVIII – subcutaneous injection licensed for Severe Haem A Monitored by a modified Factor VIII assay

Question 22

Combined FV and FVIII

Answer 22

Rare autosomal recessive bleeding disorder found around the Mediterranean sea.
Moderate bleeding tendency.
FV and FVIII levels - 5-30%.
Normally due to a mutation in transport protein .
Treatment FVIII concentrate, FFP/ Octaplas

Question 23

Factor IX

Answer 23

Haemophilia B.
1 in 50-100,000.
Similar clinical picture to Haem A. Recurrent spontaneous joint bleeds occur.
Bleeding in carriers more common.
Treatment – Berifix. Once daily. Refixia –pegulated FIX – Different assay needed.
Inhibitors are less common.
Gene Therapy

Question 24

Factor X

Answer 24

One of the rarest autosomal recessive.
Similar clinical picture to FVII.
Due to the longer half-life 36hrs treatment can be given as Prothrombin complex concentrate or FFP daily.
For major surgery FX is kept >30%. 10-40 % haemostatic.

Question 25

Factor XI

Answer 25

Also called Haemophilia C .
Ashkenazi Jews up to 13% population affected.
Heterozygous have a partial deficiency, homozygous or compound heterozygous have severe deficiency.
3 mutations majority type II or III
Type II – stop codon in exon 5. homozygous state results in levels ~1%.
Type III Phe283 is replaced with Leu (missense mutation) results in levels ~10%.
Type II/III heterozygotes result in levels ~3%

FXI deficiency can lead to excessive haemorrhage after surgery or trauma but does not cause bleeds into joints or muscles.
Bleeding can be immediate or delayed
lower limit normal range 60-70%. There is poor correlation between factor level and bleeding tendency.
Heterozygotes level is 25-70 %
Treatment needed for dental
Treatment – FFP or FXI concentrate (half life 52hrs).
Complications – thrombosis and inhibitors (type 2).

Question 26

Factor XIII

Answer 26

Rare autosomal recessive.
Homozygotes present with life long bleeding from the umbilical cord.
Spontaneous intracranial bleeds common. Spontaneous abortions in early pregnancy. Delayed wound healing.
Rate assays used for determination of factor levels.
Levels >2% will allow normal haemostasis.
Treatment is prophylactic FXIII concentrate monthly or at trauma.

Question 27

Acquired Deficiencies

Answer 27

Factor II – Autoantibody due to lupus- type anticoagulant.
Factor V – transient after surgery, transfusion or aminoglycoside antibiotics.
Factor VII – Very rare.
Factor IX – very rare associated with post partum and SLE.
Factor X – Amyloidosis.

Factor VIII - Development of inhibitors due to treatment or autoantibodies found in adults, postpartum women, immunological disorders and older patients >50 yrs. Evenly distributed between the sexes. Presentation occurs with large haematomas. Treatment involves immunosuppressants (prednisone, cyclophosphamide) and Novoseven for bleeds.

Question 28

Liver Disease

Answer 28

Liver disease - Prothrombin Time increases due to a decrease of extrinsic coagulation factors synthesised in the liver. As liver damage increases the APTT will also be affected. Also affects fibrinogen synthesis.

Question 29

Vitamin K Deficiency

Answer 29

Vitamin K deficiency - This affects the production of Vitamin K dependent factors ( FII, FVII, FIX, FX) causing an increase in the Prothrombin Time.

Question 30

Lab testing

Answer 30

Venous blood collection.
Patient identification.
Anticoagulant.
Sample collection timing.
Centrifugation.
Storage.
Chapter 16: Practical Haematology.
Laboratory variables

Question 31

CTS

Answer 31

Reduces human error.
CTS reduces health and safety risks.
Large volume of work.
Reduction in assay time.

Question 32

Prothrombin Time (PT)

Answer 32

The PT is essentially a measure of the efficiency of the EXTRINSIC clotting system – FVII in addition to FV, FX, Prothrombin and Fibrinogen.
Due to presence of excess tissue factor coagulation activation is independent from FVIII and FIX and is less influenced by AT3/heparin.
Add thromboplastin (usually an extract of rabbit brain or lung) to a patients platelet poor plasma, warm, add calcium. The time to clot formation is recorded.
Normal range depend on instrument and reagent.

10-14 seconds

Question 33

Activated Partial Thromboplastin Time
(APTT)

Answer 33

Platelet substitute and Calcium
Sensitive to 
Heparin
Factors VIII, IX, XI, XII (I, II, V, X)
Lupus Anticoagulant
Liver disease
Vit K.

30-40 seconds

Question 34

Fibrinogen.

Answer 34

Measured as Clauss or derived Fibrinogen.
Clauss Fibrinogen is based on the addition of an excess of thrombin to platelet poor plasma. The fibrinogen concentration becomes the rate-limiting factor and the clotting time is a function of the fibrinogen concentration. A calibration curve shows a shortening of the clotting time with increasing fibrinogen concentration. Clotting times can be very short so normally plasma is diluted 1/10 with factor diluent.
Not affected by heparin up to 1 U/ml, bilirubin to 21mg/dl, Hb to 375mg/dl.
May be affected by degradation products.

Question 35

Further Testing.

Answer 35

Once abnormal coagulation results have been found second line tests can be done to investigate the cause.
Thrombin Time (TT).
Reptilase Time (RT) Protamine Time.
Correction Tests.
D-Dimer assay.
Factor Assays.
Dilute Russel Viper Venom Test. Lupus anticoagulant.

Question 36

Factor Assays.

Answer 36

Calibration curve performed using known amounts of factor.
Patients plasma mixed with factor deficient plasma and the appropriate test repeated. Time taken to clot can be read from graph to determine patient factor level.
What factors?
Intrinsic factors
FVIII, FIX,FXI,FXII
Extrinsic factors
FII, FV, FVII, FX

Question 37

Anticoagulant Therapy.

Answer 37

Agents inhibiting platelet function e.g aspirin.
Warfarin.
Heparin.
Thrombin Inhibitors.
FXa inhibitors.
Thrombolytic agents e.g. streptokinase
Natural Inhibitors of Coagulation.

Question 38

Warfarin

Answer 38

Inhibits the vitamin K-dependent posttranslational modification of coagulation factors.
Before release into the circulation gamma carboxylation occurs converting ~10 glutamic acid residues in their N-terminal regions to gamma-carboxyglutamates (Gla).
This is catalysed by a carboxylase requiring O2, CO2 and the reduced form of vitamin K (vitamin KH2). During this reaction vitamin KH2 is oxidised to vitamin K epoxide which is recycled by vitamin K epoxide reductase and vitamin K reductase.
Warfarin inhibits both, limiting the degree of carboxylation.

Question 39

International Normalised Ratio (INR).

Answer 39

Monitored using the PT test.
Sensitivity of thromboplastins differ according to their source therefore the INR is used for monitoring dose.
INR is calculated according to;

			INR = PRISI

Where PR is the Prothrombin Ratio (clotting time of patient/ mean normal clotting time) and ISI is the International Sensitivity Index which is a lot specific correction factor established against the WHO reference preparation.

Question 40

Heparin.

Answer 40

Heparin complexes with Anti-Thrombin III to inhibit thrombin and increase the clotting time.
ATIII complexed to heparin is 1000-fold more efficient at binding thrombin due to a conformational change induced by heparin revealing a crucial arginine residue.
Other serine proteases are inactivated by the Heparin-ATIII complex – FXa
Chromogenic Anti-Xa assays measure the effect of the low molecular weight heparins such as Tinzaparin, Fragmin, Danaparoid and Orgaran.
Some ranges given as 0.3-0.6 U/ml.

Question 41

Direct Oral Anticoagulants

Answer 41

Thrombin inhibitor 
Dabigatran (14-17hrs)
PT^, APTT^, TT^
Xa inhibitors
Rivaroxaban (7-11hrs) 
Apixaban (8-15hrs) 
PT^, APTT^, TT not affected

Question 42

Haemophilia A

Answer 42

Haemophillia Ate

Haemophilia w Factor 8

Question 43

Haemophillia B

Answer 43

B rhymes with Christmas Tree (Xmas Tree)
Factor 9 IX
Also X linked

Question 44

Common Pathway

Answer 44

The Aim is to get to the cross (Factor 10) X

1 x 2 x 5 = 10

Question 45

Haemochromatosis

Answer 45

Autosomal recessive disorder. Excessive absorption of iron. Multi-organ disorder. Liver (cirrhosis), heart (heart myopathy), pancreas (diabetes mellitus)

Question 46

Haemosiderosis

Answer 46

Sometimes referred to as secondary haemochromatosis. None genetic cause. Focal deposition. Alcoholism or thalassaemia (blood transfusions)

Question 47

Iron overload may result from

Answer 47

hereditary haemochromatosis (a genetic disorder of iron metabolism) or from secondary haemochromotosis, an acquired form of the disease that is due to excess oral intake or absorption of iron or to repeated blood transfusions. Morbidity is mainly due to iron accumulation in the endocrine organs (especially the pancreas, gonads, and pituitary), liver, and heart.

Question 48

African iron overload

Answer 48

occurs most often in sub-Saharan Africa among people who consume an iron-rich fermented drink. A genetic component is thought to contribute to the pathogenesis of African iron overload, but no gene has yet been identified.

Question 49

Treatment of TTP

Answer 49

plasma exchange (ADAMTS13)

ADAMTS13 —also known as von Willebrand factor-cleaving protease —is a zinc-containing metalloprotease enzyme that cleaves von Willebrand factor, a large protein involved in blood clotting. It is secreted into the blood and degrades large vWf multimers, decreasing their activity.

Question 50

Treatment of HUS

Answer 50

withdrawal of drugs

Question 51

Treatment of HELLP

Answer 51

HELLP- delivery of fetus and placenta

HELLP syndrome is a complication of pregnancy

Question 52

HELLP

Answer 52

HELLP syndrome is a complication of pregnancy characterized by hemolysis, elevated liver enzymes, and a low platelet count. It usually begins during the last three months of pregnancy or shortly after childbirth. Symptoms may include feeling tired, retaining fluid, headache, nausea, upper right abdominal pain, blurry vision, nosebleeds, and seizures. Complications may include disseminated intravascular coagulation, placental abruption, and kidney failure. The cause is unknown.

Question 53

Treatment of HIT

Answer 53

cessation of heparin and administration of antithrombotic agents.

Question 54

Platelet function defects

Bernard Soulier Syndrome

Answer 54

Bernard–Soulier syndrome (BSS), is a rare autosomal recessive bleeding disorder that is caused by a deficiency of glycoprotein Ib (GpIb), the receptor for von Willebrand factor.[5] The incidence of BSS is estimated to be less than 1 case per million persons, based on cases reported from Europe, North America, and Japan. BSS is a giant platelet disorder, meaning that it is characterized by abnormally large platelets.[6]

Question 55

Platelet function defects Glansmann Thrkmbasthemia

Answer 55

Fails to bind fibrinogen.
•Platelet count is normal but no aggregation with agonists e.g. ADP, epinephrine and collagen.

Glanzmann’s thrombasthenia is an abnormality of the platelets. It is an extremely rare coagulopathy, in which the platelets contain defective or low levels of glycoprotein IIb/IIIa, which is a receptor for fibrinogen. As a result, no fibrinogen bridging of platelets to other platelets can occur, and the bleeding time is significantly prolonged.

Question 56

Secondary Haemostasis

Answer 56

End of coagulation cascade is a fibrin clot.
Extrinsic. Intrinsic. Common pathway
Fibrinolysis occurs generating plasmin which dissolves the clot. The fibrinogen split products generated prevent further clotting by inhibiting fibrin polymerisation and platelet aggregation.

Question 57

HUS

Answer 57

Hemolytic–uremic syndrome (HUS) is a group of blood disorders characterized by low red blood cells, acute kidney failure, and low platelets. Initial symptoms typically include bloody diarrhea, fever, vomiting, and weakness.

Most cases occur after infectious diarrhea due to a specific type of E. coli called O157:H7.[2] Other causes include S. pneumoniae, Shigella, Salmonella, and certain medications.[1][2][3] The underlying mechanism typically involves the production of Shiga toxin by the bacteria.[1][2] Atypical hemolytic uremic syndrome (aHUS) is often due to a genetic mutation and presents differently.[1][2] However, both can lead to widespread inflammation and multiple blood clots in small blood vessels, a condition known as thrombotic microangiopathy.[6]

Question 58

Lupus anticoagulant

Answer 58

Lupus anticoagulant is an immunoglobulin[1] that binds to phospholipids and proteins associated with the cell membrane.

Question 59

Dilute viper venom test

Answer 59

The venom contains the enzymes RVV-V and RVV-X which activate factor V and factor X,[8] which converts prothrombin into thrombin in the presence of phospholipid and calcium.[9]

In the dRVVT assay, low, rate-limiting concentrations of both Russell’s viper venom and phospholipid are used to give a standard clotting time of 30 to 40 seconds.(7) This makes the test sensitive to the presence of lupus anticoagulants, because these antibodies interfere with the clot-promoting role of phospholipid in vitro, and their presence results in a prolonged clotting time.(5) A mixing study is then performed, which consists of adding an equal volume of the patient’s plasma to normal plasma; in this study, one would expect the clotting time to be significantly shortened if there was only a deficiency of coagulation factors alone.

Question 60

Lupus Anticoagulant [LA] Screening Tests:

Kaolin Clotting Time [KCT]

Answer 60

The Kaolin Clotting Time (KCT) is essentially an Activated Partial Thromboplastin Time test but without any added phospholipid. The test relies on residual cell membrane fragments and plasma lipids to provide a Phospholipid surface for coagulation reactions.

There is no phospholipid correction step for the KCT. Instead factor deficiencies as an alternative explanation for a prolonged KCT are excluded by repeating the test with the addition of relatively large quantities of normal plasma. This will shorten the KCT by replacing any deficient clotting factor but in the presence of a coagulation inhibitor there will be no or limited correction. Similarly unfractionated heparin can usually be excluded by establishing whether the patient is on heparin or not [the thrombin time and reptilase time may be useful.]

The initial steep slope of the KCT [see the Type 1 curve below] is very important and allows the test to be simplified and used as a screening test. A test comprising 100% normal plasma and 80% normal:20% patient plasma is used and a ratio derived using the formula:

KCT Formula

A ratio of ≥1.2 is considered positive for a Lupus Anticoagulant although reference ranges should be established locally.

Question 61

PTT

Answer 61

Platelet poor plasma [PPP] is mixed with Tissue Factor (TF) (containing phospholipid) at 37°C and an excess of calcium chloride (25mM) is added to initiate coagulation. In the manual technique at the same time as the calcium is added, a stopwatch is started and stopped when the clot forms. The time taken from the addition of calcium to the formation of the fibrin clot is known as the Prothrombin Time or PT. In an automated system the formation of the clot is detected electronically but the principles are identical.

Question 62

APPt

Answer 62

The APTT in contrast to the Prothrombin Time [PT], measures the activity of the intrinsic and common pathways of coagulation.

The term ‘Thromboplastin’ in this test refers to the formation of a complex formed from various plasma clotting factors which converts Prothrombin to Thrombin and the subsequent formation of the fibrin clot.

Platelet poor plasma [PPP] is incubated at 37°C then phospholipid (cephalin) and a contact activator (e.g. Kaolin, micronized silica or ellagic acid) are added. This leads to the conversion of Factor XI [FXI] to FXIa but the remainder of the pathway is not activated as no calcium is present. The addition of calcium (pre-warmed to 37°C) initiates clotting and the timer is started. The APTT is the time taken from the addition of calcium to the formation of a fibrin clot.
Most laboratories use an automated method for the APTT in which clot formation is deemed to have occurred when the optical density of the mixture has exceeded a certain threshold (clot formation makes the mixture more opaque and less light passes through).
The diagram below shows the clotting cascade and the factors that affect the APTT are shown in blue.

Question 63

Isolated Prolonged APTT

Answer 63

Deficiencies of either Factors XII, XI, IX & VIII. However, the APTT can be normal with mild deficiencies of these clotting factors. In general the deficient factor has to be less than 20-40% of normal before the APTT is prolonged [but see comments regarding APTT incubation times.]

Contact factor deficiency e.g. pre-kallikrein deficiency, HMWK deficiency

[In multiple clotting factor deficiencies the APTT becomes prolonged with less severe reductions in factor levels.

Acquired clotting factor inhibitors - these are most commonly directed against FVIII and may occur as either autoantibodies [e.g. acquired Haemophilia A] or alloantibodies (in individuals with severe Haemophilia A following exposure to exogenous factor VIII e.g. the use of factor VIII concentrate to treat a bleed). Inhibitors against other clotting factors are rare but do occur e.g. Factor V.

Lupus anticoagulant [LA] - a LA targets phospholipid and so can result in an isolated prolongation of the APTT. Although the PT requires phospholipid the concentration of PL in the PT reagents is high and so it frequently neutralises the LA and so the PT is not prolonged.

Question 64

Deficiency of Vit K

Answer 64

Haemorrhaging disease of the newborn
Biliary obstruction
Malabsorption of K (coealic)
Vit K antagonist therapy

Question 65

ADAMTS13

Answer 65

(a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13

s von Willebrand factor-cleaving protease

Question 66

VWF

Answer 66

Von Willebrand factor
Glycoproteins
Not functioning in TTP or VW Disease

Bridges platelet adhesion and promotes latetlet aggregation.