HAEMATOLOGY: COAGULATION

Four major steps in the process of coagulation:

1. Reaction of the blood vessels
2. Formation of platelet plug
3. Coagulation Cascade
4. Fibrinolysis
Once injury to the vessel wall takes place, the wall constricts. This slows down the blood flow and
allows platelets to adhere to the vessel wall. The process of adhesion requires the presence of Von
Willebrand Factor. ADP, thromboxane A2 and other substances are released by the platelets which
stimulate aggregation.
The aggregated platelets provide a surface on which coagulation takes place. Fibrin, the final
product of the process consolidates the plug.
Fibrin is digested again by enzymes such as plasminogen, of the fibrinolytic pathway.
The Coagulation Cascade:
http://en.wikipedia.org/wiki/Coagulation#The_coagulation_cascade
SCREENING TESTS FOR HAEMOSTATIC DISORDERS
1. Patient history: Both clinical and family;
2. Physical examination: Clinical evidence of bleeding, eg bruising and petechiae;
3. Laboratory Tests.
LABORATORY TESTS:

Platelet Count

Peripheral smear morphology of platelets

Bleeding Time:
This test is an index of the early stages of clot formation which involves blood vessel
contraction and platelet aggregation. It is usually normal in patients with coagulation disorders,
ie disorders of the Coagulation Cascade.
Normal: up to 9 minutes.

Prothrombin time / INR:

PT is usually prolonged in patients with deficiencies of the extrinsic coagulation pathway
(tissue factor pathway) : Factors VII, X, V, prothrombin (II ) and fibrinogen.
Normal: 10 12 seconds. INR is a ratio of standardization of PT. (Eg. Warfarin therapeutic
monitoring)

Activated Partial Thromboplastin Time (APTT):

The APTT tests for abnormalities of the intrinsic coagulation pathway : Factors XII, XI, IX, and
VIII. Heparin typically raises APTT, but rate varies with FVIII and fibrinogen levels and other
factors. Normal: 26 40 seconds.

Mixture
When the APTT is prolonged and a mixture of the patient's and normal plasma is tested, the
time will return to normal. This is not the case if an inhibitor to any of the clotting factors is
present in the patient's plasma.

Fibrin Degradation Products (D-Dimers):

The fibrin clot is dissolved by plasmin which cleaves a series of peptide bonds in fibrin,
degrading the molecule into degredation products. An increase in FDP's or D-Dimers is an
indication of fibrinolysis and is usually positive in disorders of rampant clotting like DIC.

Specialised Tests:
1. Specific coagulation factor assays
2. Correction studies
3. Platelet function tests: Plt rich plasma of patient is exposed to a variety of agents which
stimulate normal plts to aggregate. eg. ADP, collagen, adrenaline, ristocetin. The rate of
aggregation is measured by an aggregometer.

Measurement of Von Willebrand Factor:

Immunoassay.

Inhibitor Assay

DEFECTS IN HAEMOSTASIS
1. Bleeding Disorders: Vascular Defects
Platelet Disorders
Coagulation Defects
2. Thrombosis

PLATELET DISORDERS

Can be divided into 2 groups: Quantitative and Qualitative

QUANTITATIVE DISORDERS
1. Failure of Production
Aplastic Anaemia;
Leukemia and other Bone Marrow Infiltrates;
Lack of Thrombopoeitin.
2. Ineffective Production
Megaloblastic Anaemia;
Alcohol Induced Thrombocytopaenia;
Myelodisplasia.

Diagnosis of the above-mentioned disorders:

Platelet count ;
Bone marrow biopsy.
3. Increased Destruction of Platelets
In these cases the megakaryocyte and platelet production is increased to compensate for the platelet
destruction taking place in the circulation.
Causes include: Immune;
DIC;
Thrombotic Thrombocytopaenic Purpura.
Immune Thrombocytopaenia
Pathogenesis
The platelets are coated by an auto antibody; usually IgG. This occurs by one of three mechanisms:
1. IgG binds to antigen on the platelet surface
2. IgG binds to a drug which is adsorbed on the platelet surface.
3. IgG in immune complexes binds to Fc receptors on platelet surface.
The antibody coated platelets are then removed by the reticuloendothelial system causing
thrombocytopaenia.
This disorder can be secondary to conditions such as: CLL, HIV, Lymphoma, SLE.
Drugs such as quinidine also can cause this condition.
There may be no known cause: Idiopathic Thrombocytic Purpura.
Idiopathic Thrombocytopaenic Purpura
This disorder is often seen in children and young adults.
It is thought that the autoantibody with the platelet glycoproteins GP11a / GP11b.
Clinical
Bruising, petechial rash, increased menstrual bleeding.
Usually no history of precipitating event.
Laboratory
FBC: Low platelets
Bone Marrow: Increased platelet production
Increased megakaryocytes
Mild erythroid hyperplasia if bleeding has taken place.
Platelet IgG antibodies: Increased detection.
APTT: Needs to be done to rule out Lupus Anticoagulant.
Treatment
Steroids: Suppress phagocyte activity and decrease binding of IgG.
Splenectomy: Stops removal of platelets.
Disseminated Intravascular Coagulation
Pathogenesis
This disorder is caused by the exposure of the circulating blood to procoagulant activity which
initiates the coagulation process.
This results in the formation of fibrin and the consumption of both clotting factors and platelets.

The consumption will eventually lead to severe bleeding.

Causes
1. Severe infection especially gram negative bacteria. The endotoxin damages the vascular
endothelium and activates Factor VII which could initiate coagulation.
2. Complications of pregnancy:
Abruptio placenta release of tissue factor into circulation.
Retained dead foetus intrauterine material and tissue factor is absorbed into circulation.
Septic abortion.
3. Malignancy procoagulant tumor products gain access to circulation, eg. APL-M3
4. Other causes severe trauma, snake bite.
Clinical
Severe bleeding
Hemorrhagic Tissue Necrosis: uncommon, but can occur due to occlusion of small vessels by fibrin.
Microangiopathic Hemolytic Anemia.
Laboratory
Low platelet count.
Blood Smear: Decreased platelets
Increased red cell fragmentation, due to fibrin strands crossing the vessels causing a
Microangiopathic anemia.
Prothrombin Time / INR: Prolonged (consumption of clotting factors)
APTT: Prolonged (consumption of clotting factors)
Reduced plasma fibrinogen.
A positive test for Fibrin Degradation Products or D-Dimers. ( Due to increased fibrinolysis )
Other tests: Decreased Antithrombin III
Decreased clotting factors.
Treatment
Replace clotting factors with fresh frozen plasma.
Prevent clotting: Heparin
Treat underlying disorder.
Thrombotic Thrombocytopaenic Purpura (TTP)
TTP is an acute potentially fatal disorder of unknown cause. It more often affects women and is
characterized by purpura and organ damage.
Pathogenesis
It is thought the plasma of TTP patients contain a factor which induces platelet aggregation. The
platelet aggregates lodge themselves in the microcirculation and cause vessel wall damage and
often organ damage.
Clinical
Fever
Severe thrombocytopaenia
CNS involvement
Liver damage; jaundice
Renal damage
Cardiac damage
Pancreatitis

Laboratory
Decreased platelets
Red cell fragmentation (microangiopathic anemia)
PT / INR: Normal
APTT: Normal
Fibrinogen: initially normal but may fall later.
Treatment
Transfusion of large volumes of plasma.
Increased Splenic Pooling
When there is splenic enlargement of any cause there is an increased proportion of platelets pooled
in the spleen resulting in thrombocytopaenia.

QUALITATIVE PLATELET (FUNCTION) DISORDERS

Can be divided into:
Primary: Hereditary and acquired.
Secondary
Platelet function disorders are characterized by: Normal platelet count
Long bleeding time.
The abnormality may be:
Intrinsic eg. A missing glycoprotein
Extrinsic ie. platelets are normal but cannot function due to outside factor.
Primary Hereditary Platelet Disorders:
Bernard Soulier Syndrome
Pathogenesis
Platelets fail to adhere to the sub endothelium due to a missing cell surface glycoprotein, GP1b.
GP1b binds to Von Willebrand Factor, which in turn binds to the endothelium.
Laboratory
Mild to moderate thrombocytopaenia.
Peripheral Smear: Giant Platelets
Bleeding Time: Prolonged.
Disorders of Platelet Secretion
Pathogenesis
These disorders are caused by one of the following:
1. Storage Pool disease insufficient ADP in the dense granules of the platelet.
2. Defective responsiveness to thromboxane A2 caused by impaired release of ADP.
Clinical
Usually mild bleeding
Easy bruising, mild post op bleeding.

Laboratory
Abnormal Platelet morphology
Bleeding Time: Prolonged
Impaired platelet aggregation when exposed to: collagen, adrenaline, low concentrations of ADP.
Electron Microscopy: Reveals a number of dense granules.
Therapy
Bleeding is not severe and therefore therapy is not needed. Drugs that impair platelet function such
as Asprin must be avoided.
Thrombasthaenia (Glanzmans Disease)
Autosomal recessive disorder.
Pathogenesis
Platelets are deficient in platelet associated fibrinogen and lack two glycoproteins: GPIIb and
GPIIIa.
Normal platelets form a calcium dependant GPIIb/IIIa complex to which fibrinogen, fibronectin and
Von Willebrand Factor can bind. Failure of this binding results in defective hemostatic plug
formation and a serious bleeding disorder.
Laboratory
Peripheral Smear: Platelets appear normal
Bleeding Time: Prolonged
Platelet Aggregation: Abnormal with all stimuli ADP, collagen, adrenaline, thrombin.
Von Willebrands Disease (VWD)
VWD is a common hereditary bleeding disorder.
It is caused by an abnormality of the Von Willebrand Factor.
It is autosomal dominant.
The Von Willebrand Factor
VWF is a glycoprotein
It is synthesised by the endothelial cells and megakariocytes stored in alpha granules.
Secreted from the endothelial cells and platelet alpha granules.
VEF is secreted into the plasma as large multimers which become degraded as it circulates.
Function of VWF is to:
1. Facilitate the adhesion of platelets to the subendothelium of the vessel wall. This function is
performed by the large multimers.
2. Maintain normal levels of Factor VIII. Factor VIII circulates as a complex with VWF.
Multimers of all sizes bind Factor VIII. It is thought that VWF serves as a 'carrier' for Factor
VIII; stabilizing it; increasing its half life in the plasma.
Tests for VWF
1. Concentration of the protein measured by electroimmunoassay.
Plasma is subjected to electrophoresis through gel containing antibody to VWF.
2. The size of the different multimers can be determined by SDS agarose gel electrophoresis or
crossed electrophoresis.
3. The function of VWF can be determined by:
Bleeding Time
Platelet aggregation Patients with VWD have abnormal aggregation with the stimulant

ristocetin. Ristocetin is an antibiotic which causes platelet aggregation in the presence of the
intermediate multimers of VWF.
4. APTT: Prolonged
5. Factor VIII assay: Reduced.
Types of Von Willebrands Disease
Type I and Type II:
Mild bleeding disorder. Patients can suffer from nose bleeds, increased menstrual bleeding and
increased bleeding after minor surgery.
Massive joint and tissue hemorrhage does not occur.
Type I
Characterized by a decreased plasma concentration of VWF.
Laboratory
Increased Bleeding Time
Slightly prolonged APTT
Decreased levels of Factor VIII
Reduced VWF antigen
Failure of platelets to aggregate with ristocetin.
Type IIa
Characterized by normal levels of VWF, yet platelets fail to aggregate with ristocetin.
Reduced amounts of the large and intermediate multimers of VWF.
Laboratory
Increased Bleeding Time
Abnormal aggregation with ristocetin
Normal or slightly reduced VWF
Absence of large and intermediate multimers
Normal FVIII activity.
Type IIb
Characterized by increased sensitivity to ristocetin induced aggregation.
The large multimers are decreased whereas the intermediate multimers are increased.
The endothelial cells do secrete the large multimers, but these are abnormal and disappear rapidly.
Laboratory
Increased Bleeding Time
Increased aggregation sensitivity to ristocetin
Normal or slightly reduced VWF ag.
Normal FVIII activity
Absence of the large multimers.
Type III
This is a rare disorder, characterized by no measurable VWF.
Clinical
Severe bleeding disorder.

Skeletal and joint hemorrhage very similar to Hemophilia.

Laboratory
Increased Bleeding Time
Reduced aggregation with ristocetin
Reduced FVIII activity
No measurable VWF.
Pseudo Von Willebrands Disease
Clinically this disorder resembles Type IIb disease.
The platelets are abnormal and bind the large multimers of VWF, causing aggregation.
These platelet/VWF complexes are removed from the circulation.
So, Pseudo VWD feature abnormal platelets and normal VWF; whereas VWD is characterized by
normal platelets and abnormal or low VWF.
Treatment for VWD
DDAVP: Increases VWF levels in the plasma for several hours. This treatment is useless in Type II
disorders as the VWF is abnormal.
Replacement therapy: Donor Plasma.
DISTINGUISHING VWD FROM HEMOPHILIA
VWD
HEMOPHILIA
BLEEDING TIME :
FACTOR VIII:
VON WILLEBRAND
FACTOR

Prolonged
Moderately reduced
Reduced

Normal
Severely reduced
Normal

Acquired Platelet Function Disorders:

Myeloproliferatives and Myelo Displastic Syndromes
Platelet abnormalities include:
Lack of membrane adrenergic receptors which causes abnormal adrenaline aggregation.
Abnormalities of the dense granules causing depletion of ADP.
Antibody Mediated Damage
Antibodies coating the platelets in ITP and SLE cause damage leading to increased bleeding times
and abnormal aggregation.
Macroglobinaemia and Myeloma
Increased concentration of plasma immunoglobulins coating the platelets and interferes with
aggregation.
Drugs
Aspirin: Aspirin acts on the prostaglandin synthetic pathway, which can result in defective ADP
release. Patients on aspirin have an increased bleeding time and defective platelet aggregation.

Uraemia
Accumulation of waste products interferes with platelet function. This is important in Renal disease.

COAGULATIONDISORDERS
DISORDERS
COAGULATION
COAGULATION FACTORS
All coagulation factors apart from factor VIII are synthesized in the liver.
Factors II ( prothrombin ), VII, IX, X are dependent on vitamin K for synthesis.
Factors XIII, V, XI, XII are synthesized independently of vitamin K.
http://en.wikipedia.org/wiki/Coagulation
HEREDITARY COAGULATION DISORDERS
HAEMOPHILIA A AND B
Hemophilia A: Factor VIII deficiency
Hemophilia B: Factor IX deficiency
Both disorders have similar clinical symptoms and genetic inheritance. In order to differentiate
between them, each specific coagulation factor needs to be measured.
85 % of Hemophilia patients are factor VIII deficient while 15 % have a factor IX deficiency.
Genetic Inheritance
Genetic transmission is via the X chromosome (female sex chromosome).
It is a defective recessive X-linked single gene; it's X-allele usually being dominant normal.
Thus, females ( XX ) are carriers but usually not affected by the disease.
Men ( XY ) receiving the defective gene, have no counter allele; thus are affected by the disease,
while not being able to pass it on.
http://en.wikipedia.org/wiki/Hemophilia
Three types:
Severe: < 1 % Factor VIII or IX
Moderate: 1 5 % Factor activity
Mild: 5 30 % Factor activity

Clinical symptoms
Patients bleed throughout life. They often bleed into joints and muscles causing haematomas and
haemarthroses. The first major bleed usually occurs before 18 months of age.
Mild type: easy bruising; moderate bleeding post trauma or surgery.
Laboratory diagnosis
APTT: Prolonged. Both factors are part of the intrinsic pathway.
PT / INR: Normal
Bleeding Time: Normal
Factor VIII and IX assays need to be done to establish the diagnosis.
If the Factor VIII assay shows deficient, it may be necessary to exclude a diagnosis of Von
Willebrands Disease.
Inhibitors:Approximately 15 % of Factor VIII deficient patients develop inhibitors to factor VIII. In
these cases the mix (patient plasma + control plasma) fails to correct the prolonged APTT. An
inhibitor screen can be performed to quantitate the inhibitor.
Treatment
Plasma products, cryoprecipitate, lyophilised factor concentrates.
The danger in using plasma concentrates is the transmission of viruses, eg. HIV and Hepatitis.
The risk has been reduced by: testing all donors; heat treatment of concentrates.
Detection of carriers
Carriers of Hemophilia can be detected by the calculated ratio between their Factor VIII coagulation
activity and Von Willebrand Factor.
Normal: 1.0
Carriers: < 1.5
Molecular techniques are now being used. Detection of the disease and carriers can be made by
analyzing amniotic fluid.
FACTOR XI DEFICIENCY
This disorder is less common than Hemophilia and is predominant in patients of Ashkenazic Jewish
descent.
It is autosomal recessive.
Clinical findings
Mild bleeding.
Post operative bleeding can be a problem.
Laboratory diagnosis
APTT: Prolonged
Factor XI assay: Decreased
Treatment
Prophylactic treatment with fresh frozen plasma.

FACTOR XII DEFICIENCY (PREKALLIKREIN DEFICIENCY )

Usually discovered incidentally and does not impair in vivo coagulation.
The APTT is prolonged
Factor XII assay is decreased.
FACTOR DEFICIENCIES PROLONGING THE PT / INR
Factors X, V, and II (prothrombin) prolong both the APTT and PT / INR.
Factor VII prolongs only the PT / INR.
Diagnosis is made by doing specific assays.
FACTOR VII DEFICIENCY
Disorder with minimal or mild bleeding.
If factor levels drop below 3 % serious bleeding can occur.
FACTOR V DEFICIENCY
Patients have bleeding of varying severity.
If platelet Factor V levels are also low, serious bleeding can occur.
FACTOR X AND PROTHROMBIN DEFICIENCY
This disorder can have serious bleeding episodes.
DISORDERS OF FIBRINOGEN
AFIBRINOGENAEMIA
Disorder extremely rare and is autosomal recessive.
Blood fails to clot with all screening tests and only traces of fibrinogen are detected.
Patients have little spontaneous bleed can bleed after surgery.
DISFIBRINOGENAEMIA
This disorder is autosomal dominant and is extremely rare.
The plasma from patients with this disorder consists of both normal and abnormal fibrinogen.
Patients may have symptoms of bleeding but can also suffer from thrombosis.
FACTOR XIII DEFICIENCY
Clinical
Bleeding from the umbilical stump.
Poor wound healing.
Spontaneous abortions.
Laboratory
All coagulation tests are normal.
If the plasma clot is incubated overnight in 5 M urea solution, the clot will dissolve if Factor XIII
deficiency exists.

ACQUIRED COAGULATION DISORDERS

VITAMIN K DEFICIENCY
Vitamin K is needed for the synthesis of the following clotting factors:
Factor II ( prothrombin )
Factor VII
Factor IX
Factor X
2 mcg. of vit. K is needed per kilogram of body weight daily. It come sfrom two sources: diet and
bacterial synthesis of vit. K in the intestine.
Patients with vit. K deficiency develop a bleeding tendency within 10 days.
Warfarin is a vitamin K antagonist.
Laboratory features
PT / INR: Always prolonged.
Factor VII has the shortest half life and is therefore the first factor to be affected.
APTT: Normal to prolonged.
Treatment
Vitamin K.
To monitor response repeat the INR and APTT 24 hours later.
LIVER DISEASE
Liver disease may cause bleeding problems because of:
1. Impaired synthesis of clotting factors. All clotting factors except Factor VIII are synthesized
in hepatic parenchymal cells.
2. Increased fibrinolysis: alpha 2 antiplasmin, the primary inhibitor of plasmin is also
synthesized in the liver. (plasmin is a clotting regulator which breaks down it's products.)
3. Congestive splenomegaly can occur and therefore thrombocytopaenia can develop.
4. Disseminated intravascular coagulation (DIC) may develop.
Laboratory diagnosis
INR / PT: Prolonged
APTT: Prolonged
Fibrinogen: Reduced
Fibrin Degradation Products (D dimers): Positive in DIC
Therapy
Vitamin K
Fresh frozen plasma
Cryoprecipitate

ANTIBODIES TO FACTORS
These can develop in patients with hereditary clotting factor deficiencies. The patient's immune
system reacts to administered clotting factors as though they were foreign.
Antibodies can also develop in autoimmune disorder such as SLE.
Laboratory diagnosis
A mixture of normal and patient's plasma fails to correct the APTT.
Factor VIII antibodies
Can be seen in:
Hemophilia
Post partum women
Patients with immune disorders such as rheumatoid arthritis.
Laboratory
The lab. findings resemble those found in Hemophilia A.
There is a prolonged mixture and a high titre of Factor VIII antibody.
Treatment
Immunosuppressive agents in patients other than those with hemophilia.
The Lupus Anticoagulant
5 -10 % of SLE (systemic lupus erythrematous) patients develop plasma antibodies which inhibit
the phospholipid used in the APTT test.
Patients with this disorder often have reduced platelets.
This antibody is not only found in patients with SLE but also other diseases such as:
Immune disorders
Patients on certain drugs such as quinine.
Clinical features
Patients do not bleed abnormally but often have increased thrombosis.
It has been associated with spontaneous abortions.
Laboratory features
APTT: Prolonged and does not correct with the mixture.
PT / INR: Normal or slightly prolonged.
Special tests: By adding a synthetic phospholipid mixture to the APTT system, the time can be
corrected. This is the Kaolin Clotting Time.
THROMBOSIS
Thrombosis occurs when there is a breakdown in the balance between thrombogenic factors and
protective mechanisms. This results in an abnormal mass which can lead to vascular occlusion.
Thrombogenic factors include:
Damage to the vessel wall
Stimulation of platelet aggregation
Activation of blood coagulation.

Failure of protective mechanisms:

Deficiency of natural coagulation inhibitors: Antithrombin III, Protein S and C
Reduced hepatic clearance of activated clotting factors.
Defective fibrinolysis.
Thrombosis usually occurs in vessels where the normal blood flow has been disturbed. These can be
veins (Deep vein thrombosis DVT) or artery (Arterial thrombosis).
There are variety of causes:
Protein C deficiency
Protein C is vitamin K dependant and is synthesized in the liver.
It inhibits the active forms of Factor V and Factor VIII.
Activation of Protein C occurs via thrombin bound to a protein called thrombomodulin.
Clinical features
Patients have recurrent venous thromboses from an early age.
Diagnosis
Protein C assay: Reduced
Protein S deficiency
The anticoagulant activity of protein C requires a co-factor which is Protein S. Prot. S is also
vitamin K dependant.
Clinically patients suffer from thromboses from an early age.
Diagnosis is made by measuring the amount of Protein S.
Antithrombin III deficiency
Antithrombin III is a potent inhibitor of factors XII, XI, X, IX, VIII.
Deficiencies can lead to recurrent thrombosis.
Activated Protein C Resistance
Protein C acts on Factor V and inhibits its function. If Factor V is resistant to this action, patients
have an increased risk of thrombosis.
This disorder is known as APC resistance or Factor V Leiden.
Diagnosis is made by detecting the abnormality at molecular level using PCR.
This disorder is thought to be a major cause of thrombosis in young adults.
TREATMENT OF THROMBOSIS
1. Anti thrombotic therapy: Aim is to induce fibrinolysis and dissolve the clot.
Examples: Streptokinase, Urokinase
2. Anti coagulants: This is the first line of therapy. Anticoagulants can be used to:
Treat a current thrombosis,
Prevent further thrombosis
Anticoagulant therapy is monitored by the INR and APTT.
The INR is used to monitor warfarin therapy: Therapeutic range is 2.0 4.0
The APTT is used to monitor Heparin therapy.

BLEEDING DISORDERS

VASCULAR DEFECTS
Vascular disorders are a heterogenous group of conditions which are characterized by bruising and
spontaneous vessel bleeding.
The abnormality is caused either by damage to:
A) The vessels themselves
B) The perivascular connective tissue.
Clinical
Symptoms are not severe.
Bleeding is usually into the skin; can also be from mucous membranes.
Laboratory tests
Main screening test is Bleeding Time, which can often be normal.
INHERITED VASCULAR DISORDERS
Inherited Telangiectasia
Pathogenesis
The abnormality lies in the sub-endothelial connective tissue which results in abnormally dilated
blood vessels.
Clinical
Telangiectasia appears in both the skin and mucous membranes.
Bleeding may be from the gastrointestinal tract.
Anemia may develop due to blood loss.
Laboratory
Bleeding Time: Normal
Other Inherited Vascular Disorders are extremely rare and consist of:
Ehlers Danlos Syndrome
Osteogenesis imperfecta
Pseudoxanthoma elasticum
These are all characterized by vascular fragility.
ACQUIRED VASCULAR DISORDERS
Simple Easy Bruising ( Purpura Simplex )
This disorder occurs mainly in women. The cause is unknown but an increase in vessel fragility is
thought to be responsible.

Clinical
Recurrence of unexplained bruises.
Diagnosis
Made on clinical features.
Other bleeding disorders need to be ruled out.
Senile Purpura
Occurs commonly in elderly people.
The histology of the affected skin shows marked atrophy of collagen.
Purpura Post Infection and Drugs
The Purpura is thought to be caused by toxic damage to the vascular endothelium.
A number of drugs have been implicated.
The Purpura clears after removal of the drug.
Other rare acquired vascular defects:
Hanloch Schonlein Syndrome: ? Hypersensitivity.
Scurvy: Vitamin C is necessary for collagen formation.

Notes are from Cape Pen. University of Technology (Fmr. Cape Technikon), 2002, ND., B.Tech.:
Biomedical Technology.
More Course notes at :
http://www.scribd.com/document_collections/2374607