Pathy's Principles and Practice of Geriatric Medicine. Группа авторов

Pathy's Principles and Practice of Geriatric Medicine - Группа авторов


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23.1). DIC is characterized by great variation both between patients and within the same patient over time. It is a dynamic condition that will progress if untreated but can rapidly improve with appropriate treatment of the underlying cause. Recognition and treatment of the underlying cause are more important in treating DIC than support with haemostatic factors and platelets – giving more coagulation factors, fibrinogen, and platelets without treating the cause results in more substrate for uncontrolled coagulation and more microvascular thrombosis and end organ damage. Due to its severity and dynamic nature, it has been difficult to perform adequate randomized controlled trials in the management and treatment of DIC, although there have been several recent advances in its early diagnosis and treatment.3

      Clinically, DIC manifests as simultaneous bleeding and microvascular thrombosis leading to multiple organ dysfunction, including acute kidney injury (AKI), adult respiratory distress syndrome (ARDS), and hepatic and neurological dysfunction, and is often associated with fever, hypotension, lactic acidosis, hypoxia, and proteinuria. While bleeding is the most obvious and commonly recognized manifestation, death by bleeding is rare due to the use of blood and platelet transfusions in the treatment of hypovolaemia. The usual cause of death in DIC is multiorgan failure as a consequence of microvascular thrombosis, which is not immediately clinically apparent. Treatment of multiorgan failure, which is a consequence of anoxia and ischaemic necrosis of vital organs, is far more difficult to treat satisfactorily.5

Schematic illustration of mechanism of microvascular thrombosis and bleeding in DIC. Broken lines indicate inhibition.
Mechanism Example
Coagulation cascade activation Tissue factor exposure in trauma and extensive surgery
Fibrinolytic cascade activation Plasminogen activators liberated in acute promyelocytic leukaemia or disseminated prostatic cancer
Intravascular platelet aggregation Haemolytic uraemic syndrome, thrombotic thrombocytopenic purpura, heparin‐induced thrombocytopenia
Endothelial cell activation Gram‐negative sepsis, disseminated malignancy
Direct proteolytic cleavage of haemostatic proteins Pancreatitis, snake venoms

      The bleeding in DIC is multifactorial in origin as a result of depletion of fibrinogen, all coagulation factors, and platelets as a consequence of consumption due to uncontrolled and excessive activation of the coagulation cascade, diminished platelet number due to consumption, and an additional or acquired platelet defect consequent to proteolytic degradation of platelet surface glycoproteins and partial degranulation of α and dense platelet granules. Hyperfibrinolysis leads to elevated levels of fibrinogen and fibrin degradation products (measured as highly increased D‐dimers), which act as competitive inhibitors of fibrin polymerization. The uncontrolled generation of free thrombin and plasmin degrades fibrin, fibrinogen, and coagulation factors, particularly factors V and VIII. Consequently, there is a systemic bleeding diathesis resulting in not only bleeding from local surgical incisions or traumatic wounds but also generalized bruising, petechiae, and purpura, together with bleeding from sites of venepuncture, arterial lines, drains, catheters, and endotracheal tubes. There is also frequent gastrointestinal bleeding, haemoptysis, haematuria, and even intramuscular or intracerebral bleeding. Clinically, the widespread occurrence of abnormal and excessive bleeding is the hallmark of DIC. Excessive bleeding from a single site, particularly following surgery, is usually more indicative of a specific failure of local haemostasis than DIC and requires specific local measures. The microvascular thrombosis results in anoxic damage and ischaemic infarction of vital organs, including lungs, kidneys, brain, pituitary, liver, adrenal, heart, and skin.6

Test Result
APTT Prolonged >10 seconds beyond normal
PT Prolonged > 5 seconds beyond normal
TT Prolonged > 10 seconds beyond normal
Fibrinogen Low, usually <1 g l−1
Platelets Low, usually <50 × 109 l−1
D‐dimer Raised > 1000 ng/ml

      As


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