ACQUIRED COAGULATION ABNORMALITIES

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ACQUIRED COAGULATION ABNORMALITIES
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ACQUIRED COAGULATION ABNORMALITIES - causes

• 1. Vitamin K deficiency
• 2. Liver disease
• Clotting factor inhibitors
• circulating anticoagulants
• complications of anticoagulant therapy
• 4. Incraesed consumption or loss of the
  clotting factors
• a) disseminated intravascular coagulation (
  DIC)
• b) fibrinogenolysis (primary
  fibrinolysis)

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Coagulation abnormalities of vitamin K deficiency

• vitamin K is essential for the final
  postribosomal carboxylation of F II, VII, IX, X
  and the physiologic anticoagulants, protein C and
  protein S
• Laboratory features
• ? PT (prothrombin time) and ? F II, VII, IX, X
• aPTT (activated partial thromboplastin time) may
  be prolonged in severe, protracted vitamin K
  deficiency
• Levels of PIVKA-II (Proteins induced in vitamin K
  absence) are more sensitive than PT

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Vitamin K deficiency-etiology

• I. Inadequate supply
• 1. Dietary deficiency (leafy green vegetables
  90-120mcg)
• 2. Destroying the gut flora by administration
  of broad-spectrum antibiotics
• II. Impaired absorption of vitamin K
• 1. Biliary obstruction (gallstone,
  strictures, tumor)
• 2. Malabsorption of vitamin K(sprue, celiac
  disease, ulcerative colitis)
• 3. Drugs (cholestyramine)
• III. Pharmacologic antagonists of vitamin K
  (coumarins, warfarin)

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Abnormalities of hemostasis and coagulation in
liver diseases (1)

• I. Decreased synthesis of coagulation factors
• 1. Fibrinogen, protrombin, clotting F V, VII,
  IX, X, XI, XII, XIII, prekallikrein, high
  molecular weight kininogen
• 2. Antiplasmins, antithrombin, protein C and
  protein S
• II. Aberrant biosynthesis
• 1. Of abnormal fibrinogenu
• 2. Of abnormal analogues of prothrombin, F
  VII, IX, X

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Abnormalities of hemostasis and coagulation in
liver diseases (2)

• III. Deficient clearance
• 1. Of fibrin monomers, fibrinogen
  degradation products (FDP)
• 2. Of activated coagulation factors (IXa,
  Xa, Xia)
• 3. Of plasminogen acivators
• IV. Accelerated destruction of coagulation
  factors
• 1. Intravascular coagulation
• 2. Localized coagulation (hepatic cell
  necrosis)
• 3. Abnormal fibrinolysis
• V. Thrombocytopenia and platelet dysfunction
  (splenomegaly)

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Treatment

• Vitamin K doses 10mg
• FFP (invasive procedure)
• Prothrombin complex concentrates
• Platelet transfusion
• Antifibrynolytic agents (dental extraction)

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Circulating anticoagulants

• Clotting factor inhibitors are
• autoantibodies (usually IgG) or
  alloantibodies (in hemophilia A)
• that inactivate coagulation factors
• - Laboratory test prolonged aPTT

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Circulating anticoagulants

• I. Antibodies to factor VIII (prolonged aPTT,
  normal INR)
• 1. In hemophilia A
• 2. Postpartum -several months after
  parturition in asociation with a first pregnancy
• 3. Various immunologic disorders (rheumatoid
  arthritis, SLE, penicillin allergy)
• 4. Older patients without underlying disease
• II. Other spontaneous inhibitors (rarely)-
  against factors V, IX, XIII, fibrinogen,
• III. Lupus anticoagulant (in 30 SLE, rheumatoid
  arthritis, HIV infection, in lymphoproliferative
  disorders, after drugs hydralazine, quinidine,
  penicillin)

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Acquired hemophilia A

• Common bleeding sites are
• soft tissue, skin, and mucous membrane
• Treatment Factor VIII bypassing agents
• Recombinant activated factor VII
• Plasma-derived factor eight-inhibitor bypassing
  agent
• (FEIBA, also called activated prothrombine
  complex concentrate)
• To eradicate the inhibitor is recommended

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Disseminated intravascular coagulation

DIC

• is an acquired syndrome characterized by
• systemic intravascular activation of
  coagulation,
• leading to fibrin deposition in the
  microvasculature
• and small-vessels, contributing to organ
  dysfunction
• consumption of platelets and coagulation factors
• lead to thrombocytopenia and impaired
  coagulation
• and may result in bleeding
  complications

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Clinical conditions that may be complicated by DIC

• Severe alergic/toxic reaction
• Obstetrical conditions
• Amniotic fluid embolism
• Abruptio placentae
• HELLP syndrome
• Solid tumors

• Sepsis/severe infection
• Trauma
• Malignancy
• Acute leukemias
• Kasabach-Merritt syndrome
• Vascular abnormalities

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ACUTE DIC-CLINICAL PRESENTATION

• symptoms of underlying disease
• symptom of local thrombosis
• hemorrhagic diathesis
• shock

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Diffuse intravascular

coagulationMicrothrombosis secondary
fibrinolysis ? platelets


FDP clotting
factors Ischemic tissue damage
Microangiopathic Bleeding

anemia
tendency



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Acute DIC - laboratory features

• ? Increased D-Dimer level
• ? FDP level
• ? AT level
• ? platelet level
• Bload smear - schistocytes
• ? fibrinogen level
• ? TT (Thrombin time)
• ? aPTT
• ? PT (Prothrombin time)

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Acute DIC diagnosis

• The basis of the diagnosis is the knowledge of
  the underlying diseases
• Patients suffering from acute DIC need urgent
  therapy
• DIC should always be taken into consideration if
  a complex coagulation defect in combination with
  a underlying disease is observed

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Diagnostic algorithm for the diagnosis of overt
DIC (1)

• Risk assessment
• Does the patient have an underlying disorder
  known to be associated
• with overt DIC?
• If yes, proceed

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Diagnostic algorithm for the diagnosis of overt
DIC (2)

• - Order global
  coagulation tests
• Platelet count
• (gt1000, lt1001, lt502)
• Elevated fibrin-related markers
• (FDP no increase0, moderate increase2,
  strong increase3)
• Prolonged PT
• (lt3sec. 0, gt3 but lt6 1, gt6sec. 2)
• Fibrinogen level (gt1g/L0, lt1g/L1)
• If 5 compatible
  with overt DIC

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CHRONIC (compensated) DIC

• In chronic DIC, the activation of the
  hemostatic system is minimal since negative
  feedback mechanisms as well as inhibitors can
  limit the activation process so that microthrombi
  do not occur and bleeding episodes are rare
  phenomena

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Chronic DIC - etiology

• 1. Obstetric complications eclampsia, the death
  fetus syndrom
• 2. Vascular disorders
• giant hemangiomas (Kasabach Merrit syndrome),
  Leriche
• syndrome, Raynaud,s disease
• 3. Carcinomas
• 4. Hematology disorders myelofibrosis,
  polycythemia vera, PNH
• 5. Reumathoid disorders SLE, sclerodermia
• 6. Kidneys disorders glomerulonephritis, HUS
• 7. Another vasculitis allergica, diabetes
  mellitus

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PRIMARY FIBRINOLYSIS (FIBRINOGENOLYSIS)

• DEFINITION
• primary fibrinolysis occurs when plasmin is
  generated in the absence of DIC
• ? This has been described in hepatic disorders,
  prostatic carcinomas, and cases without apparent
  cause
• ? At present, most cases of primary fibrynolysis
  are iathrogenically induced during thrombolytic
  therapy

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Plasminogen intrinsic
extrinsic
exogenous activation
activation
activationfactor XIa, XIIa, kallikrein
tPA, uPA
streptokinasekininogen

or APSAC PlasminFibrino
gen FibrinFDP FDP
D-Dimer
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Acquired coagulation abnormalities - diagnostics

• I History
• II Physical examination
• III Laboratory features
• - morphology
• - blood smear
• - bleeding time
• - prothrombin time (PT), INR
• - aPTT
• - thrombin time (TT)
• - fibrinogen
• - fibrin(ogen) degradation products (FDP)
• - D-dimer
• - antithrombin

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PT aPTT
Platelet Fibrinogen TT FDP D-Dimer
AT
count Acute
DIC ? ? ?
? ? ?
? ? Chronic DIC
N ? N ? N ? N ?
? N ? ? ?
? Fibrinogenolysis N ?
? N ? ?
N N N
Heparin overdosage ? ?
N N N
N N N Dicumarol
? N? N
N ? N
N N
overdosage or


prothrombin complex


factors defficiency
Diferentiation of aquired coagulation
abnormalities
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ACA DIC THERAPY

• 1. Treatment of the underlying disorder
• 2. Treatment of shock
• 3. Replacement therapy
• - platelet concentrates
• - RBC
• - FFP
• - Cryoprecipitate (fibrinogen)
• - Activated protein C (drotrecogin alfa)
• Heparin treatment
• unfractioned heparin or low-molecular
  weight heparin
• acrocyanoza, purpura fulminans, dermal
  necrosis, venous thromboembolism

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Treatment thrombosis predominantes

• Continous infusion of UFH
• Prophilactic doses of heparin or LMWH
• Especially, severe purpura fulminans,
• acral ischemia, vascular skin infarction

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Treatment - bleedings

• Transfusion of platelets or plasma (components)
  including FFP and/or prothrombin complex
  concentrate (fluid overload)
• Severe hipofibrynogeneamia (lt1g/L)
• FFP, fibrionogen concentrate and
  cryopercipitate

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CASE PRESENTATION