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
• 3. Clotting factor inhibitors
• a) circulating anticoagulants
• b) 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 vitamin K deficiency
dependent

• vitamin K is essential for the final
  postribosomal carboxylation of coagulation
  factors II, VII, IX, X and the physiologic
  anticoagulants, protein C and protein S
• laboratory features - prothrombin time (PT) is
  prolonged and decreased factors II, VII, IX, X
  level
• activated partial thromboplastin time (aPTT) -
  prolonged in severe, protracted vitamin K
  deficiency

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Vitamin K deficiency-etiology

• I. Inadequate supply
• 1. Dietary deficiency
• 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 factors
  V, VII, IX, X, XI, XII, XIII, prekallikrein, high
  molecular weight
• kininogen
• 2. Antiplasmins, antithrombin, protein C and
  S
• II. Aberrant biosynthesis
• 1. Of abnormal fibrinogenu
• 2. Of abnormal analogues of prothrombin,
  factors 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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Circulating anticoagulants

• Clotting factor inhibitors are autoantibodies
  (usually IgG) or alloantibodies ( in hemophilia
  A) that inactivate coagulation factors and,
  therefore, act as anticoagulants
• - The 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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Disseminated intravascular coagulation - DIC

• DIC is an acquired syndrome characterized by the
  activation of intravascular coagulation up to
  intravascular fibrin formation.,The process may
  be accompanied by secondary fibrinolysis or
  inhibition of fibrinolysis. This definition
  implies that microclot formation and consecutive
  organ failure and/or a hemorrhagic diathesis may
  occur.

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DIC- ETIOLOGY

• 1. Infections viral (herpes, acute hepatitis),
  bacterial (meningococcemia, septicemia), mycotic
  (aspergillosis), protozoal (malaria),
• 2. Abruptio placentae, septic abortion,
  postpartum hemolytic-uremic syndrome
• 3. Neoplasms carcinomas (prostate, pancreas,
  lung, ovary)
• 4. Disorders of hematopoietic systemacute
  leukemia (promyelocytic ) intravascular hemolysis
  
• 5. Vascular disorders giant hemangiomas,
  aneurysmas, myocardial infarctioncardiac arrest,
  various forms of shock,
• 6. Massive tissue injury large traumatic
  injuries and burns,
• 7. Miscellaneous acute pancreatitis, graft
  versus host disease, diabetic acidosis,

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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
coagulationMicrot
hrombosis secondary fibrinolysis
? platelets

FDP
clotting factors Ischemic
tissue damage
Microangiopathic Bleeding

anemia
tendency



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AcuteDIC-laboratory features

• Increased D-Dimer level
• Increased FDP level
• Decreased AT level
• Decreased platelet level
• Bload smear - schistocytes
• Decreased fibrinogen level
• Prolonged thrombin time
• Prolonged aPTT
• Prolonged prothrombin time (PT)

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Acute DIC diagnosis

• The basis of the diagnosis is the knowledge of
  the underlying diseases in which DIC can occur.
  Because 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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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, NNH
• 5. Collagen-vascular 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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FIRINOLYSIS
Plasminogen intrinsic
extrinsic
exogenous activation
activation
activationfactor XIa, XIIa,
kallikrein tPA, uPA
streptokinasekininogen

or APSAC
PlasminFibrinogen Fibrin
FDP 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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Diferentiation of aquired coagulation
abnormalities
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
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ACA THERAPY (1)

• I Vitamin K deficiency
• - Vit. K i.m. / i.v. 10-20 mg/doba
• - severe bleeding - Vit.K i.v. FFP(?) 10-15
  ml/kg
• II Liver disease
• - Vit. K
• - severe bleeding FFP or prothrombin complex
  concentrates (FEIBA, Autoplex)
• III Warfarin overdosage
• - withhelt anticoagulant on 1-2 d, reduction of
  dosage
• - moderate complications Vit,. K
• - severe bleeding FFP or prothrombin complex
  concentrates, FFP

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ACA- Therapy (2)

• IV Bleeding disorders of circulating inhibitors -
  factor VIII inhibitor
• - massive FVIII replacement , cryoprecipitate
• - FVIII porcin
• - immunosuppressive therapy
• - plasmapheresis and high dose i.v. IgG
• - activated FVII
• V Heparin-induced hemorrhage stop the heparin
  infusion, intravenous protamin administration at
  the dosage of 1mg/100U of heparin, FFP

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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
• 4. Heparin treatment (unfractioned heparin or
  low-molecular weight heparin (acrocyanoza,
  purpura fulminans, dermal necrosis, venous
  thromboembolism)