Infringements of coagulability of system of
blood
Infringements of coagulability of system of blood
Infringements of a hemostasis, a coagulopathy- infringement of function of coagulative and anticoagulative systems of a blood.
Coagulation
Coagulation is a complex process by which blood forms clots.
Hemostasis
•Primary (platelets form a plug at the site of injury
•Secondary (proteins in the blood plasma respond in a complex cascade to form fibrin strands, which strengthen the platelet plug)
Regulators of anticoagulation•Protein C is a vitamin K-dependent
serine protease enzyme that is activated by thrombin into activated protein C (APC).
•Antithrombin is a serine protease inhibitor (serpin) that degrades the serine proteases.
•Tissue factor pathway inhibitor (TFPI) limits the action of tissue factor (TF).
Regulators of anticoagulation•Plasmin is generated by proteolytic
cleavage of plasminogen, a plasma protein synthesized in the liver.
•Prostacyclin (PGI2) is released by endothelium and activates platelet Gs protein-linked receptors.
•Fibrinolysis
Testing of coagulationCommon:- aPTT- PT- Fibrinogen testing- Platelet count- Platelet function testing
Other:- TCT- Bleeding time- Coagulation factor assays- Antiphosholipid antibodies- D-dimer
Influence of surgery trauma on hemostasis
•Damage to tissues exposes subendothelium proteins
•Proteins in the blood plasma, called coagulation factors or clotting factors, respond in a complex cascade to form fibrin strands
•Immobilization – slow down of the blood flow
Risk factors for postoperative thrombosis
Perioperative, exposing factors affecting risk include:
• Dehydration • Postoperative
immobilisation • Need for transfusion
Patient-related, or predisposing, risk factors include:
• Inherited thrombophilia • Advanced age • Obesity• Cancer• Prior VTE• Varicose veins • Use of estrogen-containing
medications (such as oral contraceptives and hormone replacement therapy)
Measures of prophylactics of thrombosis
•low molecular weight heparins (LMWH)•Early and regular ambulation (walking)•Intermittent pneumatic compression (IPC)•150-300 mg of aspirin
DIC - is a complex systemic thrombohemorrhagic disorder involving
the generation of intravascular fibrin and the consumption of procoagulants and platelets. The resultant clinical condition is characterized by intravascular
coagulation and hemorrhage.
Epidemiology
•½ of DIC cases result from complications of pregnancy.
•1/3 result from carcinomatosis.
•1/6 make up all other causes.
2 forms of DICAcute Chronic
• develops acutely when sudden exposure of blood to procoagulants occurs
• Compensatory hemostatic mechanisms are quickly overwhelmed
• Abnormalities of blood coagulation parameters are readily identified
• organ failure frequently occurs
• develops when blood is continuously or intermittently exposed to small amounts of tissue facto
• Compensatory mechanisms in the liver and bone marrow are not overwhelmed
• little obvious clinical or laboratory indication
• observed in solid tumors and in large aortic aneurysms
Causes of DIC
•Acute vs Chronic•Systemic vs Localized•Single vs Multiple conditions
Acute DIC
•Infectious•Malignancy •Obstetric
Infectious Bacterial (eg, gram-negative sepsis, gram-
positive infections, rickettsial) Viral (eg, HIV, cytomegalovirus [CMV],
varicella, hepatitis) Fungal (eg, Histoplasma) Parasitic (eg, malaria)
Malignancy Hematologic (eg, acute myelocytic
leukemias) Metastatic (eg, mucin-secreting
adenocarcinomas)
Obstetric Placental abruption Amniotic fluid embolism Acute fatty liver of pregnancy Eclampsia
Acute DIC▫Trauma ▫Burns ▫Motor vehicle accidents (MVAs) ▫Snake envenomation ▫Transfusion ▫Hemolytic reactions
Acute DIC▫Massive transfusion ▫Liver disease - Acute hepatic failure ▫Prosthetic devices ▫Shunts (Denver, LeVeen) ▫Ventricular assist devices
Chronic DIC▫Malignancies
Solid tumors Leukemia
▫Obstetric Retained dead fetus syndrome Retained products of conception
Chronic DIC▫Hematologic
Myeloproliferative syndromes Paroxysmal nocturnal hemoglobinuria
▫Vascular Rheumatoid arthritis Raynaud disease
Chronic DIC▫Cardiovascular
Myocardial infarction
▫Inflammatory Ulcerative colitis Crohn disease Sarcoidosis
Localized DIC▫Aortic aneurysms ▫Giant hemangiomas (Kasabach-Merritt
syndrome) ▫Acute renal allograft rejection ▫Hemolytic uremic syndrome
Pathophysiology
•increased thrombin generation•a suppression of anticoagulant pathways•impaired fibrinolysis• inflammatory activation
The DIC process can be divided into four stages•Hypercoagulable (Stage I) •Secondary fibrinolytic (Stage II) •Hypocoagulable (Stage III) •Reparation stage
Hypercoagulable (Stage I)•release of tissue factor (TF)•FVIIa activation of the extrinsic pathway•deposition of thrombin in the
microcirculation system•microthrombosis of the capillaries of
major organs, leading to Acute Respiratory Distress Syndrome , multiple organ failure (MOF), miscarriage, clotted graft, pulmonary embolism (PE), acute myocardial infarct (AMI), stroke, and deep vein thrombosis (DVT).
Secondary fibrinolytic (Stage II)• release of TPA by the endothelium system,
which activates plasminogen to plasmin• Plasmin breaks down the clot, releasing
fibrinogen degradation product (FDP)• release of TPA is an attempt to
counterbalance the prothrombotic state into normal hemostasis and to prevent deposition of thrombi into the microcirculatory system
• FDP, acts as an anticoagulant to inhibit platelet aggregation and prevent normal cross-linking of fibrin
Hypocoagulable phase (Stage III)•leads to hemorrhage, but can be treated
by FFP, cryo, and platelets to stop the bleeding
•allogenic blood products, in addition to exposing the patient to donor blood products and the risk of blood-borne diseases, also initiates strong inflammatory reactions
Reparation phase
•Normalization of all body functions•Blood tests, condition of the patient are
repairing to normal
Diagnosis
•Severe cases with haemorrhage▫PT and APTT are prolonged▫fibrinogen level markedly reduced▫High levels of fibrin degradation products,
including D-dimer▫severe thrombocytopenia▫blood film may show fragmented red blood
cells
Diagnosis
•Mild cases without bleeding:▫increased synthesis of coagulation factors
and platelets▫PT, APTT, and platelet counts are normal▫fibrin degradation products are raised
Definitive diagnosis
•Thrombocytopenia•Prolongation of prothrombin time and
activated partial thromboplastin time•low fibrinogen concentration•Increased levels of fibrin degradation
products
Treatment
•Reversal of the underlying cause•Anticoagulants•Platelets•Fresh frozen plasma•Infusion with antithrombin