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Acquired Coagulation Acquired Coagulation DisordersDisorders

Dr Mohammed Saiem Al-dahrDr Mohammed Saiem Al-dahr

KAAUKAAU

Faculty of Applied Medical Faculty of Applied Medical SciencesSciences

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Acquired coagulation disordersAcquired coagulation disorders

ObjectivesObjectives Following this lecture, the student will be able toFollowing this lecture, the student will be able to Explain the classification of acquired disorder of Explain the classification of acquired disorder of

haemostasis such as:haemostasis such as: Hepatic disease, vitamin K deficiency, renal disease, Hepatic disease, vitamin K deficiency, renal disease, Explain the action of oral anticoagulantsExplain the action of oral anticoagulants Name the most common laboratory tests used to monitor Name the most common laboratory tests used to monitor

oral anticoagulant therapyoral anticoagulant therapy List mechanisms and clinical conditions associated with List mechanisms and clinical conditions associated with

DICDIC.. Define the three generalized clinical states of Define the three generalized clinical states of DICDIC Laboratory abnormalities associated with Laboratory abnormalities associated with DICDIC.. Identify therapies for treatment of Identify therapies for treatment of DICDIC

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Acquired coagulation disordersAcquired coagulation disorders

The normal haemostasis is a The normal haemostasis is a normal balancenormal balance carefully designed so that carefully designed so that hemorrhagehemorrhage arrested arrested and inappropriate and inappropriate thrombosisthrombosis does not occur. does not occur.

Acquired disordersAcquired disorders of haemostasis occur with of haemostasis occur with many, many, systemic diseasessystemic diseases, , drugsdrugs, physical states , physical states pregnancy pregnancy and and newbornsnewborns..

Diagnosis depends onDiagnosis depends on;; Careful historyCareful history Physical ExaminationPhysical Examination Properly directed lab tests.Properly directed lab tests.

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Acquired coagulation disordersAcquired coagulation disorders

The initial difficulty is to distinguish local The initial difficulty is to distinguish local bleeding e.g. peptic ulcer from systemic disease.bleeding e.g. peptic ulcer from systemic disease.

An initial series of screening tests are performed An initial series of screening tests are performed easily and rapidly;easily and rapidly;

Platelet count + Blood filmPlatelet count + Blood film Bleeding time (BT)Bleeding time (BT) Prothrombin Time (PT)Prothrombin Time (PT) Partial Thromboplastin Time (PTT)Partial Thromboplastin Time (PTT) Thrombin Time (TT)Thrombin Time (TT) Assessment of FibrinogenAssessment of Fibrinogen

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Acquired coagulation disordersAcquired coagulation disorders

If screening is If screening is suggestivesuggestive, specific special , specific special investigations are performed to confirm, the investigations are performed to confirm, the diagnosis.diagnosis.

The acquired disordersThe acquired disorders of haemostasis that will of haemostasis that will be discussed here include the following;be discussed here include the following;

Hepatic DiseaseHepatic Disease Vitamin K deficiencyVitamin K deficiency Vitamin K AntagonistsVitamin K Antagonists Renal DiseaseRenal Disease DICDIC

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Acquired Coagulation DisordersAcquired Coagulation Disorders

Hepatic DiseaseHepatic Disease The liver is the principal site of synthesis of pro-The liver is the principal site of synthesis of pro-

coagulant, fibrinolytic, and coagulation inhibitory coagulant, fibrinolytic, and coagulation inhibitory proteins. proteins.

Liver disorders present Liver disorders present twotwo challenges: challenges: 1-Decreased synthesis of coagulation1-Decreased synthesis of coagulation, , lysis and lysis and inhibitory proteinsinhibitory proteins2-Impaired clearance of activated haemostatic 2-Impaired clearance of activated haemostatic components.components.

The type of disorder differs in neonates and The type of disorder differs in neonates and adults.adults.

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Acquired coagulation disordersAcquired coagulation disorders

NeonatesNeonates display display decreased levels of decreased levels of plasma plasma contactcontact factors secondary to factors secondary to hepatic immaturityhepatic immaturity. .

They also They also lack lack sufficient levels of sufficient levels of Plasminogen Plasminogen and anti-Thrombin III. and anti-Thrombin III.

NeonatesNeonates express a unique express a unique fetal fibrinogenfetal fibrinogen that that does not behave in the same manner as does not behave in the same manner as adult adult fibrinogenfibrinogen, and they have , and they have decreased of decreased of fibrinogenfibrinogen..

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Acquired coagulation disordersAcquired coagulation disorders

In adultsIn adults, liver diseases, such as cirrhosis, , liver diseases, such as cirrhosis, hepatitis, and diseases that infiltrate liver tissue, hepatitis, and diseases that infiltrate liver tissue, such as neoplasm, affect the such as neoplasm, affect the synthetic capacity of synthetic capacity of the liverthe liver..

Prolongation of the PTProlongation of the PT is considered a sign of is considered a sign of worsening disease because of worsening disease because of depression vitamin depression vitamin K-dependent factor synthesisK-dependent factor synthesis, poor dietary intake , poor dietary intake or mal-absorption of or mal-absorption of vitamin Kvitamin K. .

Fibrinolytic events and thrombocytopenia may Fibrinolytic events and thrombocytopenia may accompany liver disease.accompany liver disease.

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Acquired Coagulation DisordersAcquired Coagulation Disorders

Laboratory FindingsLaboratory Findings Screening tests such as the Screening tests such as the PT, APTT, TT, PT, APTT, TT,

bleeding Time, platelet count, fibrinogen levels, bleeding Time, platelet count, fibrinogen levels, and FDPand FDP determinations are used to monitor determinations are used to monitor haemostatic status in liver disease patients.haemostatic status in liver disease patients.

TherapyTherapy Infusion of Infusion of fresh plasmafresh plasma may increase the may increase the

circulating levels of pro-coagulants and minimize circulating levels of pro-coagulants and minimize the hemorrhagic risk. the hemorrhagic risk.

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Acquired coagulation disordersAcquired coagulation disorders

Vitamin K DeficiencyVitamin K Deficiency For coagulation factors (For coagulation factors (II, VII, IX, and XII, VII, IX, and X) to ) to

become active they have to bind become active they have to bind CalciumCalcium.. This is This is preceded by preceded by carboxylationcarboxylation which is mediated by which is mediated by Vitamin KVitamin K

Vitamin KVitamin K Is fat soluble vitamin, stored in the liver in small Is fat soluble vitamin, stored in the liver in small

amounts so can be depleted in 2-3 daysamounts so can be depleted in 2-3 days

Patients with depleted vitamin K or on K Patients with depleted vitamin K or on K antagonists antagonists cannot carboxylatecannot carboxylate these coagulation these coagulation factors.factors.

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Acquired coagulation disordersAcquired coagulation disorders

Vitamin KVitamin K is necessary co-factor for the is necessary co-factor for the conversionconversion of terminal of terminal glutamicglutamic acid acid residues to residues to gamma-carboxyglutamicgamma-carboxyglutamic acid on factors acid on factors II, VII, II, VII, IX, X, as well as on protein C & SIX, X, as well as on protein C & S

This conversion takes place in the hepatocyte This conversion takes place in the hepatocyte and is necessary for proper function.and is necessary for proper function.

Laboratory finding.Laboratory finding. PT PT prolongedprolonged PTTPTT prolonged prolonged Functional assays of vitamin Functional assays of vitamin KK factors show low factors show low

levellevel

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Acquired coagulation disordersAcquired coagulation disorders

Vitamin K AntagonistsVitamin K Antagonists Oral anticoagulantsOral anticoagulants

Mechanism of ActionMechanism of Action

All the vita K-dependent coagulation proteins, (F All the vita K-dependent coagulation proteins, (F II, VII, IX, X, proteins S and C)II, VII, IX, X, proteins S and C) are characterized are characterized in theirin their structure by specific chain where some structure by specific chain where some glutamic acidglutamic acid residues undergo residues undergo a gamma-a gamma-carboxylationcarboxylation..

This This gamma-carboxylationgamma-carboxylation is vitamin K-dependent. is vitamin K-dependent. The presence of The presence of carboxylatedcarboxylated groups is necessary groups is necessary

for the binding of for the binding of CaCa ions ions required for the required for the formation of the various activation complexes formation of the various activation complexes during the activation of the coagulation.during the activation of the coagulation.

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Acquired coagulation disordersAcquired coagulation disorders

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Acquired coagulation disordersAcquired coagulation disorders

The classic The classic oral anticoagulantoral anticoagulant (Warfarin) (Warfarin) presents a structural presents a structural similarity with vitamin Ksimilarity with vitamin K

Therefore, these anticoagulant are able to Therefore, these anticoagulant are able to inhibit inhibit thethe regeneration step of reduced vitaminregeneration step of reduced vitamin K. K.

The The inhibition of the reduced vitamin K by inhibition of the reduced vitamin K by anticoagulants blocks the final synthesis step of anticoagulants blocks the final synthesis step of these vitamin K dependent proteins.these vitamin K dependent proteins.

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Acquired coagulation disordersAcquired coagulation disorders

LaboratoryLaboratory The most common laboratory test to monitor oral The most common laboratory test to monitor oral

anticoagulant therapy is the anticoagulant therapy is the PTPT It is sensitive to the decrease of factors It is sensitive to the decrease of factors II, VII, XII, VII, X.. PTPT does not reflect the effect of the drug on does not reflect the effect of the drug on

factor factor IXIX..To promote standardization of the To promote standardization of the PTPT for for monitoring oral anticoagulant therapy,monitoring oral anticoagulant therapy,

HWOHWO has developed an international reference has developed an international reference thromboplastin from human brain tissue and has thromboplastin from human brain tissue and has recommended that the recommended that the PT ratioPT ratio expressed as the expressed as the International Normalized Ratio (International Normalized Ratio (INR).INR).

INRINR value for a plasma depends on the value for a plasma depends on the international sensitivity index (ISI).international sensitivity index (ISI).

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Acquired coagulation disordersAcquired coagulation disorders

Renal DiseaseRenal Disease.. In acute and chronic renal diseases there is often In acute and chronic renal diseases there is often

bleeding tendency associated several bleeding tendency associated several haemostatic abnormalities.haemostatic abnormalities.

Thrombocytopenia frequently develop in uremiaThrombocytopenia frequently develop in uremia Vitamin K deficiency due to malnutrition, Vitamin K deficiency due to malnutrition,

associated liver disease with factor V deficiencyassociated liver disease with factor V deficiency..

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Acquired coagulation disordersAcquired coagulation disorders

Isolated factors Isolated factors IX and XIIIX and XII deficiency were deficiency were reported in nephrotic syndromereported in nephrotic syndrome

excessive loss of these proteins in the urine.excessive loss of these proteins in the urine. Antithrombin III and plasminogenAntithrombin III and plasminogen are also lost in are also lost in

nephrotic syndrome through increased nephrotic syndrome through increased urinary urinary lossloss..

Patients with renal disease commonly have:Patients with renal disease commonly have: A prolonged bleeding time (BT)A prolonged bleeding time (BT) Prolonged Prolonged PTPT and and PTTPTT Low platelet countLow platelet count AnemiaAnemia