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