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Acquired Coagulation Disorders

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Acquired Coagulation Disorders Dr Mohammed Saiem Al-dahr KAAU Faculty of Applied Medical Sciences Acquired coagulation disorders Objectives Following this lecture ... – PowerPoint PPT presentation

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Title: Acquired Coagulation Disorders


1
Acquired Coagulation Disorders
  • Dr Mohammed Saiem Al-dahr
  • KAAU
  • Faculty of Applied Medical Sciences

2
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

3
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.

4
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

5
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

6
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.

7
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.

8
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.

9
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.

10
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.

11
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

12
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.

13
Acquired coagulation disorders
14
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.

15
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).

16
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.

17
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
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