Pathology Seminar October 2010 Year 4 MedicineGroup 1 UST Sana’a
Introduction DIC stands for Disseminated intravascular coagulation. It is the disturbance of the blood clotting mechanism. Several clots in some vessels increase consumption of the blood clotting factors and platelets deficiency, lack or destruction of those factors in other body parts Several bleedings in other areas of the body.
Normal Hemostasis During vascular injury hemostasis normally occurs on the affected site. The hemostasis has four phases: 1. Vasoconstriction then, 2. Primary phase, 3. Secondary phase, 4. Tertiary phase,
VASOCONSTRICTIONAfter vascular injury occurs there are certainfactors of neurohumoral type released causingtransient vasoconstriction to the affected site.
PRIMARY HEMOSTASISPlatelets adhere (via GpIb receptors) to exposedextracellular matrix by binding to von Willebrand factorand are activated, undergoing a shape change and granulerelease. Released adenosine diphosphate and thromboxaneA2 lead to further platelet aggregation (via binding offibrinogen to platelet GpIIb-IIIa receptors), to form theprimary hemostatic plug.
SECONDARY HEMOSTASISLocal activation of the coagulation cascade (involvingtissue factor and platelet phospholipids) results infibrin polymerization, "cementing" the platelets into adefinitive secondary hemostatic plug.
TERTIARY HEMOSTASISCounter-regulatory mechanisms, such as release of t-PA (Tissue plasminogen activator, a fibrinolyticproduct) and thrombomodulin (interfering with thecoagulation cascade), limit the hemostatic process tothe site of injury.
1) Generation of a hyperthrombinemic state2) Alteration of the physiological anticoagulants levels3) Impaired fibrinolysis at the onset of the DIC:4) Activation and liberation of inflammatory cytokines in the pathogenesis of DIC
Generation of a 1) hyperthrombinemic state The exposing of the tissue factors thromboplastin and factor III during injury causes a cascade activation of a factor pathway that has a dominant role in the hyperthrombinemic state in DIC. Cytokines and bacterial endotoxin are all triggers to the formation of endothelial cell tissue factor. In severe trauma also tissue phospholipids initiates the clotting cascade.
Alteration of the physiological2)anticoagulants levels There are 3 most common Anticoagulants in the body: Antithrombin, Active Protein C Tissue factor pathway inhibitor (TFPI). In DIC: ↓Antithrombin ↓Active Protein C
Impaired fibrinolysis at the onset of3)the DIC: Plasminogen activator inhibitor 1 (PAI-1) is a neurohumoral compound released by the endothelial cells at the effected site. PAI-1 suppresses the normal fibrinolysis activity. Some DIC individuals have shown a mutation in the PAI-1 gene, leading to an increased plasma PAI-1 levels.
Activation and liberation of inflammatory4)cytokines Activation of Clotting sys. Inflammatory cascade activation Induced pro-inflammatory cytokines (thrombin and other serine proteases). Pro-inflammatory cytokines + Protease-activated receptors (of the cell surface of the endothelial cells) Inducing an inflammatory and clotting reaction.
Signs & symptoms of DIC Renal failure. Cough Confusion. Decreased platelets. Blood clots. Drop in blood pressure. Sudden bruising. Bleeding, possibly from multiple sites in the body. Fever
Sites of Thrombosis Site in decreasing order of frequency Brain Heart Kidney Adrenals Spleen Lungs Liver
DIC Is most likely to occur after sepsis, obstetric complications, malignancy, and major trauma (especially trauma to the brain)
1. CBC2. Clotting times:3. Fibrin related markers important for the diagnosis of DIC:4. Coagulation factors:
Labinvestigations of DICCBCthrombocytopenia is usually presentClotting times: Prothrombin time (PT) – prolonged (may be normal in early or chronic DIC)Partial thromboplastin time (PTT) – prolonged (may be normal in early orchronic DIC)Thrombin time (TT) – may be increased due to consumption of fibrinogenFibrin related markers important for the diagnosis of DIC:D-dimer – increased in acute and chronic DIC (best single test)A normal d-dimer essentially rules out DICElevated d-dimer levels are seen in a number of conditions in addition to DIC(eg, pregnancy, acute thrombosis)Coagulation factors:Fibrinogen is usually decreased (in an acute phase of DIC, the fibrinogen may notbe decreased, only until DIC is severe)
International Society onThrombosis and HaemostasisScoring System for Diagnosis ofDICA score below 5 issuggestive as adiagnosis but notdefinite; hence thetest must berepeated.
Treatment The most important fact in the management of DIC, is the treatment of the underlying cause. Supportive therapy may be given to patients with excessive bleeding: 1) Fluid 2) Blood transfusion 3) Fresh frozen plasma 4) Platelet concentrates 5) Fibrinogen Patients with chronic DIC and thrombosis may need heparin therapy.