Which coagulation factors are not made in the liver

Activated by collagen, disrupted basement membranes, activated platelets, and high molecular weight kininogen and prekallikrein in conjunction with factor XI. PTT but not PT is prolonged in severe deficiency. No bleeding diathesis associated with its congenital deficiency. High molecular weight kininogen and prekallikrein Fletcher factor : Clotting factors that activate the early phase of the intrinsic pathway and the complement system. No bleeding diathesis associated with their congenital deficiencies.

Stabilizes polymerized fibrin in the presence of calcium. In its absence, clots are soluble in 5-molar urea. Quantitation of clotting factors can be achieved through assays specific for each factor, whether chromogenic or, more commonly, automated clotting tests. A plasma deficient in each factor is purchased and used to find out whether it corrects the patient's plasma. When there is correction, the patient's defect has been identified and can be quantitated using a reference curve obtained with dilutions of normal pooled plasmas.

These four factors are quantitated in assays that use PT reagents as activators. To measure blood heparin factor Xa inhibition and possibly when therapeutic inhibitors of factor X are used therapeutically. Factor VII: Pregnancy and oral contraceptive use.

An increase in factor VII has been linked to thrombophilia in some studies. Factor VIII: Acute-phase reactant acute inflammatory conditions , pregnancy, and the use of oral contraceptives. If markedly increased, it may predispose to thromboembolism. Factor IX: Pregnancy and use of oral contraceptives. Very elevated values have been associated with a tendency to thromboembolism.

Factor X: Pregnancy and use of oral contraceptives. Congenital deficiency recessive inheritance : Bleeding of various severities in homozygotes. Acquired deficiency: Liver disease, DIC, pathologic fibrinolysis, vitamin K deficiency, or warfarin therapy. The liver is responsible for producing most of these coagulation factors. Some of these factors require vitamin K for synthesis, and the liver produces the bile salts essential for intestinal absorption of this fat-soluble vitamin.

Uncontrolled bleeding may occur if the clotting factors are not produced or if vitamin K is not absorbed. The liver produces most of the proteins found in blood. Albumin is a major protein made by the liver that plays an important role in regulating blood volume and distribution of fluids in the body.

One possible result of liver dysfunction is low albumin levels, which can lead to abnormal fluid retention causing swollen legs and abdominal distension. The liver also produces ferritin a protein used to store iron in the body as well as proteins that bind to hormones, lipoproteins involved in cholesterol transport, and acute phase proteins involved in inflammation and infection.

The liver has many key functions associated with hormones in the body. For example, the liver is involved in the chemical conversion of thyroid hormone into its most active form. In addition, the liver secretes IGF-1, a hormone that promotes cell growth.

Angiotensinogen is another hormone produced by the liver. This hormone is part of a complex system that regulates sodium and potassium levels in the kidneys and is involved in blood pressure control. In addition, the liver regulates hormone levels by breaking down and removing these chemical messengers from the body when they are no longer needed.

Together with the spleen, the liver helps to degrade old red blood cells into breakdown products, such as bilirubin and other bile pigments. The liver extracts these products from the blood for elimination via urine and stool. When the liver fails to function properly, bilirubin may accumulate in the body and result in a yellow appearance of the skin and eyes, known as jaundice.

The liver also plays a large role in detoxifying and breaking down toxic poisons, drugs, alcohol, and waste products. Factor VIII is synthetised mainly by hepatic sinusoidal endothelial cells, but also by endothelial and non-parenchymal cells in the kidney, spleen, lungs, and brain.

Thus, the plasma concentration of factor VIII is not decreased with liver disease, and may even be increased, because many chronic liver diseases are associated with inflammation. Vitamin K promotes hepatic post-ribosomial conversion of glutamic acid residues in protein precursors, to gamma-carboxyglutamic acid Gla forms that chelate calcium and allow effective hemostatic function. When gamma-carboxylation is impaired due to deficiency or antagonism of vitamin K, inert precursers are synthesized, known as proteins induced by vitamin K absence [PIVKA] and released into the blood.

In cholestasis, reduction of vitamin K absorption from the small intestine due to decreased bile salt production can be treated by parenteral administration of vitamin K 10mg daily for 24 to 48 hours. In parenchymal liver disease, decreased levels of coagulation and inhibitor proteins are the result of decreased synthesis, and so there is often no improvement with vitamin K administration.

In acute liver failure, the first factors whose plasma concentrations fall are those with the shortest half-lives, factor V and VII 12 and 4 to 6 hours, respectively.

The synthesis of vWF, an acute phase reactant, is increased in tissue injury, and in endotoxemia associated with endothelial dysfunction. In chronic liver disease, increased shear stress of endothelial cells related to portal hypertension may also contribute to the high plasma levels of vWF. Plasma fibrinogen is also an acute-phase reactant, but usually remains normal or increased in patients with liver disease.

This causes a prolonged thrombin time TT , despite almost normal PT and PTT partial thromboplastin time values, with a normal concentration of antigenic fibrinogen.

This acquired dysfibrinogenemia is reversed following recovery of liver function. Thrombocytopenia has not been associated with an increased risk of bleeding from esophageal varices or other sites although there are only few studies evaluating this , but does correlate with blood loss during surgery. The issue of sequestration versus other causes of thrombocytopenia in cirrhosis has been evaluated recently by comparing platelet number in extrahepatic portal hypertension, to that of cirrhotics with a similar size spleen.

There was less severe thrombocytopenia in the non-cirrhotic patients. The liver produces thrombopoietin TPO , which regulates platelet production in the bone marrow. Acute infection with hepatitis C virus HCV , alcohol abuse, and folate deficiency can all contribute to myelosuppression, further lowering platelet counts.

DIC disseminated intravascular coagulation does not commonly influence platelet counts in cirrhosis. Thrombocytopenia may sometimes also result from immune-mediated mechanisms. Platelet function, as well as decreased platelet number, may be impaired in patients with liver disease.

Platelet aggregation in response to ADP adenosine diphosphate , arachidonic acid, collagen, and thrombin may be subnormal, probably due to a defective signal transduction pathway. Synthesis of anticoagulant factors is decreased in patients with liver disease. Antithrombin III ATIII is a non-vitamin K-dependent glycoprotein synthesized by the liver and endothelium that is reduced in plasma concentration in patients with liver disease, probably predominantly due to decreased synthesis.

Proteins C and S are vitamin K-dependent glycoproteins synthesized mainly by hepatocytes. When there is severe liver disease, it can be difficult to exclude coexistent genetic deficiency, because levels may be very low due to decreased synthesis. Protein C deficiency is not associated with extrahepatic portal vein thrombosis. All the proteins involved in fibrinolysis, except for tPA tissue plasminogen activator and PAI-1 plasminogen activator inhibitor-1 , are synthesized in the liver.

Reduced plasma levels of plasminogen, alpha 2 a2 -antiplasmin, histidine-rich glycoprotein HRG , factor XIII, and thrombin-activable fibrinolysis inhibitor TAFI, a carboxypeptidase occur in patients with liver cirrhosis.

Conversely, tPA levels are increased in liver disease due to decreased clearance, and the tPA inhibitor, PAI-1, is normal or only slightly increased in plasma.

The inhibitor concentrations are insufficient to counteract the increase in tPA, accounting for a net increase in fibrinolysis. In contrast, in patients with acute liver failure, there are high levels of the acute phase reactant PAI-1 and hypofibrinolysis. Hyperfibrinolysis is correlated with the severity of liver cirrhosis, as assessed by Child-Pugh score. Ascitic fluid also has increased fibrinolytic activity. Many studies using different methodologies demonstrate hyperfibrinolysis thromboelastography, diluted whole blood clot lysis assay, and euglobulin clot lysis time.

Other studies have not confirmed hyperfibrinolytic activity in cirrhosis. There may be a correlation between hyperfibrinolysis and an increased risk of variceal bleeding.

In addition, increased fibrinolytic activity during liver transplantation and hepatic resection correlates with blood loss. Patients with cholestatic liver disease have higher PAI-1 concentrations, and this offsets their increased tPA activity.

The clinical result is less hyperfibrinolysis in the reperfusion phase during liver transplantation, and antifibrinolytic therapy is not usually administered.

Disseminated intravascular coagulation DIC is characterized by intravascular fibrin deposition due to activation of the clotting cascade that overwhelms anticoagulation mechanisms. Secondary to the activation of the coagulation pathway, consumption of coagulation factors and platelets, associated with secondary fibrinolysis, occurs and causes an increased bleeding tendency. Low grade DIC and hemostatic abnormalities present in cirrhotic patients that share common laboratory features prolonged PT and PTT, low fibrinogen level, elevated fibrin-degradation products and D-dimer, and thrombocytopenia , and can be confused with each other.

Early reports linked chronic liver disease to low grade DIC with accelerated fibrinolysis. However, the presence of DIC in liver cirrhosis is currently disputed. In contrast to these results, Ben Ari, et al. TEG studies were, however, able to detect hyperfibrinolysis. AICF may be important in the portal venous system, as the phenomenon is more pronounced there, than in systemic blood. These are factors ii , vii , ix , and x , the factors of the so-called prothrombin complex.

Unable to display preview. Download preview PDF. Skip to main content. This service is more advanced with JavaScript available. Advertisement Hide. Blood Coagulation and Liver Function. Authors Authors and affiliations E. This process is experimental and the keywords may be updated as the learning algorithm improves. This is a preview of subscription content, log in to check access. Bowie, E. Thrompson, P. Didisheim, C. Owen, Disappearance rates of coagulation factors: transfusion studies in factor-deficient patients.

Transfusion , 7, Britten, A. Salzman, Surgery in congenital disorders of blood coagulation.