Acquired Coagulation Disorders

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Acquired Coagulation Disorders

• Dr Mohammed Saiem Al-dahr
• KAAU
• Faculty of Applied Medical Sciences

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Acquired coagulation disorders

• Objectives
• Following this lecture, the student will be able
  to
• Explain the classification of acquired disorder
  of haemostasis such as
• Hepatic disease, vitamin K deficiency, renal
  disease,
• Explain the action of oral anticoagulants
• Name the most common laboratory tests used to
  monitor oral anticoagulant therapy
• List mechanisms and clinical conditions
  associated with DIC.
• Define the three generalized clinical states of
  DIC
• Laboratory abnormalities associated with DIC.
• Identify therapies for treatment of DIC

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Acquired coagulation disorders

• The normal haemostasis is a normal balance
  carefully designed so that hemorrhage arrested
  and inappropriate thrombosis does not occur.
• Acquired disorders of haemostasis occur with
  many, systemic diseases, drugs, physical states
  pregnancy and newborns.
• Diagnosis depends on
• Careful history
• Physical Examination
• Properly directed lab tests.

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Acquired coagulation disorders

• The initial difficulty is to distinguish local
  bleeding e.g. peptic ulcer from systemic disease.
• An initial series of screening tests are
  performed easily and rapidly
• Platelet count Blood film
• Bleeding time (BT)
• Prothrombin Time (PT)
• Partial Thromboplastin Time (PTT)
• Thrombin Time (TT)
• Assessment of Fibrinogen

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Acquired coagulation disorders

• If screening is suggestive, specific special
  investigations are performed to confirm, the
  diagnosis.
• The acquired disorders of haemostasis that will
  be discussed here include the following
• Hepatic Disease
• Vitamin K deficiency
• Vitamin K Antagonists
• Renal Disease
• DIC

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Acquired Coagulation Disorders

• Hepatic Disease
• The liver is the principal site of synthesis of
  pro-coagulant, fibrinolytic, and coagulation
  inhibitory proteins.
• Liver disorders present two challenges
• 1-Decreased synthesis of coagulation, lysis and
  inhibitory proteins
• 2-Impaired clearance of activated haemostatic
  components.
• The type of disorder differs in neonates and
  adults.

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Acquired coagulation disorders

• Neonates display decreased levels of plasma
  contact factors secondary to hepatic immaturity.
• They also lack sufficient levels of Plasminogen
  and anti-Thrombin III.
• Neonates express a unique fetal fibrinogen that
  does not behave in the same manner as adult
  fibrinogen, and they have decreased of fibrinogen.

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Acquired coagulation disorders

• In adults, liver diseases, such as cirrhosis,
  hepatitis, and diseases that infiltrate liver
  tissue, such as neoplasm, affect the synthetic
  capacity of the liver.
• Prolongation of the PT is considered a sign of
  worsening disease because of depression vitamin
  K-dependent factor synthesis, poor dietary intake
  or mal-absorption of vitamin K.
• Fibrinolytic events and thrombocytopenia may
  accompany liver disease.

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Acquired Coagulation Disorders

• Laboratory Findings
• Screening tests such as the PT, APTT, TT,
  bleeding Time, platelet count, fibrinogen levels,
  and FDP determinations are used to monitor
  haemostatic status in liver disease patients.
• Therapy
• Infusion of fresh plasma may increase the
  circulating levels of pro-coagulants and minimize
  the hemorrhagic risk.

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Acquired coagulation disorders

• Vitamin K Deficiency
• For coagulation factors (II, VII, IX, and X) to
  become active they have to bind Calcium. This is
  preceded by carboxylation which is mediated by
  Vitamin K
• Vitamin K
• Is fat soluble vitamin, stored in the liver in
  small amounts so can be depleted in 2-3 days
• Patients with depleted vitamin K or on K
  antagonists cannot carboxylate these coagulation
  factors.

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Acquired coagulation disorders

• Vitamin K is necessary co-factor for the
  conversion of terminal glutamic acid residues to
  gamma-carboxyglutamic acid on factors II, VII,
  IX, X, as well as on protein C S
• This conversion takes place in the hepatocyte and
  is necessary for proper function.
• Laboratory finding.
• PT prolonged
• PTT prolonged
• Functional assays of vitamin K factors show low
  level

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Acquired coagulation disorders

• Vitamin K Antagonists
• Oral anticoagulants
• Mechanism of Action
• All the vita K-dependent coagulation proteins, (F
  II, VII, IX, X, proteins S and C) are
  characterized in their structure by specific
  chain where some glutamic acid residues undergo a
  gamma-carboxylation.
• This gamma-carboxylation is vitamin K-dependent.
• The presence of carboxylated groups is necessary
  for the binding of Ca ions required for the
  formation of the various activation complexes
  during the activation of the coagulation.

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Acquired coagulation disorders
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Acquired coagulation disorders

• The classic oral anticoagulant (Warfarin)
  presents a structural similarity with vitamin K
• Therefore, these anticoagulant are able to
  inhibit the regeneration step of reduced vitamin
  K.
• The inhibition of the reduced vitamin K by
  anticoagulants blocks the final synthesis step of
  these vitamin K dependent proteins.

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Acquired coagulation disorders

• Laboratory
• The most common laboratory test to monitor oral
  anticoagulant therapy is the PT
• It is sensitive to the decrease of factors II,
  VII, X.
• PT does not reflect the effect of the drug on
  factor IX.
• To promote standardization of the PT for
  monitoring oral anticoagulant therapy,
• HWO has developed an international reference
  thromboplastin from human brain tissue and has
  recommended that the PT ratio expressed as the
  International Normalized Ratio (INR).
• INR value for a plasma depends on the
  international sensitivity index (ISI).

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Acquired coagulation disorders

• Renal Disease.
• In acute and chronic renal diseases there is
  often bleeding tendency associated several
  haemostatic abnormalities.
• Thrombocytopenia frequently develop in uremia
• Vitamin K deficiency due to malnutrition,
  associated liver disease with factor V deficiency.

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Acquired coagulation disorders

• Isolated factors IX and XII deficiency were
  reported in nephrotic syndrome
• excessive loss of these proteins in the urine.
• Antithrombin III and plasminogen are also lost in
  nephrotic syndrome through increased urinary
  loss.
• Patients with renal disease commonly have
• A prolonged bleeding time (BT)
• Prolonged PT and PTT
• Low platelet count
• Anemia