Acquired coagulation factor deficiency

Hematology

Clinicals - History

Fact Explanation
Neonates with symptoms of hemorrhages (as described below) The transmission of maternal vitamin K to the fetus is limited during the pregnancy, so the newborns have a low liver stores of it.Hemorrhagic disease of the newborn manifests early following birth and can cause fatal hemorrhages. It's customary to give paraentral vitamin K megadose to the infants soon after birth to prevent the complications . Special attention should be given to mothers who took antiepileptic medications during pregnancy. Even though the typical scenario is to present with bleeding early, there have been reported cases of late hemorrhagic disease of the newborn , some of them have been given prophylactic vitamin K too. Neonates with symptoms of hemorrhages (as described below)
The transmission of maternal vitamin K to the fetus is limited during the pregnancy, so the newborns have a low liver stores of it.Hemorrhagic disease of the newborn manifests early following birth and can cause fatal hemorrhages. It's customary to give paraentral vitamin K megadose to the infants soon after birth to prevent the complications . Special attention should be given to mothers who took antiepileptic medications during pregnancy. Even though the typical scenario is to present with bleeding early, there have been reported cases of late hemorrhagic disease of the newborn , some of them have been given prophylactic vitamin K too.
A history of ingesting oral anticoagulant drugs. Vitamin K is an important factor in post-translational modifications of coagulation factors II, VII, IX and X. oral anticoagulants, widely known warfarin, is an Vit K antagonist, so blocks this action, causing low levels of above mentioned coagulation factors. Symptoms start manifesting a week or so later, following starting of therapy since already manufactured coagulation factors are still circulating. Bleeding can be manifested in various sites. A history of ingesting oral anticoagulant drugs.
Vitamin K is an important factor in post-translational modifications of coagulation factors II, VII, IX and X. oral anticoagulants, widely known warfarin, is an Vit K antagonist, so blocks this action, causing low levels of above mentioned coagulation factors. Symptoms start manifesting a week or so later, following starting of therapy since already manufactured coagulation factors are still circulating. Bleeding can be manifested in various sites.
Chronic diarrhea. Vitamin K absorption is linked with fat absorption. As a result the conditions leading to fat malabsorption, leads to vitamin K deficiency and following that, coagulation factor deficiency. Chronic diarrhea.
Vitamin K absorption is linked with fat absorption. As a result the conditions leading to fat malabsorption, leads to vitamin K deficiency and following that, coagulation factor deficiency.
A history of liver disorder. Usually chronic liver diseases more than acute ones. Vitamin K is a fat-soluble essential vitamin and needs bile for it's absorption. Bile is synthesized by the liver and when hepatocytes are damaged, and once the half-time of already existing Vitamin K is spent, acquired Vitamin K deficiency and resulting acquired coagulation factor deficiency occurs. The clotting factors themselves are also synthesized by the liver, so there is a gross deficiency of them in liver diseases. Even the synthesized ones are also functionally subnormal. Some liver pathologies like hepatic portal hypertension are associated with spelenomegaly and hypersplenism, so the resulting thrombocytopenias are also causative factors of coagulation deficits. A history of liver disorder.
Usually chronic liver diseases more than acute ones. Vitamin K is a fat-soluble essential vitamin and needs bile for it's absorption. Bile is synthesized by the liver and when hepatocytes are damaged, and once the half-time of already existing Vitamin K is spent, acquired Vitamin K deficiency and resulting acquired coagulation factor deficiency occurs. The clotting factors themselves are also synthesized by the liver, so there is a gross deficiency of them in liver diseases. Even the synthesized ones are also functionally subnormal. Some liver pathologies like hepatic portal hypertension are associated with spelenomegaly and hypersplenism, so the resulting thrombocytopenias are also causative factors of coagulation deficits.
A history of massive transfusion of blood. massive blood transfusion is defined as transfusion of at least 5 units of blood in 4 hours. There is a hemodilution and secondary clotting factor deficiency and thrombocytopenia. A history of massive transfusion of blood.
massive blood transfusion is defined as transfusion of at least 5 units of blood in 4 hours. There is a hemodilution and secondary clotting factor deficiency and thrombocytopenia.
No family history of coagulation factor deficiency. i. e. Hemophilias Which is the differentiating factor from congenital coagulation factor deficiencies. This is usually due to presence of inhibiting factors for coagulation components. No family history of coagulation factor deficiency. i. e. Hemophilias
Which is the differentiating factor from congenital coagulation factor deficiencies. This is usually due to presence of inhibiting factors for coagulation components.
A history of ingesting an offending drug. i.e. antibiotic, psychotrophic or immunomodulatory drug. The reaction to the drug causes formation of inhibitors to coagulation factors. Over 30 drugs have been documented causing this reaction. A history of ingesting an offending drug. i.e. antibiotic, psychotrophic or immunomodulatory drug.
The reaction to the drug causes formation of inhibitors to coagulation factors. Over 30 drugs have been documented causing this reaction.
A probable triggering factor. i.e. pregnancy, autoimmune disease flare up, malignancy or infection In most cases a probable triggering factor can be identified. A probable triggering factor. i.e. pregnancy, autoimmune disease flare up, malignancy or infection
In most cases a probable triggering factor can be identified.
Sudden episodes of bleeding tendencies The patients usually present with no previous family or personal history of bleeding manifestations and sudden bleeding episodes in varying sites of the body. Sudden episodes of bleeding tendencies
The patients usually present with no previous family or personal history of bleeding manifestations and sudden bleeding episodes in varying sites of the body.

Clinicals - Examination

Fact Explanation
Evidence of bleeding into skin, mucus membranes, soft tissues and muscles. Congenital hemophilia is characterized by bleeding into joint spaces leading to hemarthrosis, but in acquired types, it's rarely seen. Instead, bleeding into skin (purpura, ecchymosis) mucus membranes (purpura) soft tissues (subcutaneous bruising) and muscles (tender swelling of muscles) is present. It's usually more severe than congenital type bleeding. In most of the cases bleeding is spontaneous. Evidence of bleeding into skin, mucus membranes, soft tissues and muscles.
Congenital hemophilia is characterized by bleeding into joint spaces leading to hemarthrosis, but in acquired types, it's rarely seen. Instead, bleeding into skin (purpura, ecchymosis) mucus membranes (purpura) soft tissues (subcutaneous bruising) and muscles (tender swelling of muscles) is present. It's usually more severe than congenital type bleeding. In most of the cases bleeding is spontaneous.

Investigations - Diagnosis

Fact Explanation
Platelet count As a part of complete blood cell count. Platelets are a component in primary hemostasis. In bleeding disorders that are due to coagulation factors, platelet count is essentially normal. Platelet count
As a part of complete blood cell count. Platelets are a component in primary hemostasis. In bleeding disorders that are due to coagulation factors, platelet count is essentially normal.
Liver function profile Since the liver disorders are one of the commonest reasons for coagulopathy , liver function screening should be done in all patients presenting with bleeding disorders. Liver function profile
Since the liver disorders are one of the commonest reasons for coagulopathy , liver function screening should be done in all patients presenting with bleeding disorders.
Bleeding time BT is a tool to assess platelet function , and by that, primary hemostasis. Where thrombocytopenia is not a prominent feature, bleeding time is usually normal. Bleeding time
BT is a tool to assess platelet function , and by that, primary hemostasis. Where thrombocytopenia is not a prominent feature, bleeding time is usually normal.
Prothrombin time/ Inernational Normalized Ratio PT evaluates the extrinsic pathway of coagulation cascade (which assesses the factors VII, X, V, II, and fibrinogen) and INR standardizes it. It's prolonged in patients on anticoagulant therapy, liver disease, vitamin K deficiency and DIC. Prothrombin time/ Inernational Normalized Ratio
PT evaluates the extrinsic pathway of coagulation cascade (which assesses the factors VII, X, V, II, and fibrinogen) and INR standardizes it. It's prolonged in patients on anticoagulant therapy, liver disease, vitamin K deficiency and DIC.
Activated Partial Thromboplastin Time (APTT) aPTT is a screening tool in coagulation disorders. It assesses intrinsic pathway of the coagulation cascade and elevated in vitamin K deficiency, hemophilias, vWF deficiency, liver diseases and other isolated coagulation factor deficiencies. In acquired type of coagulopathies the change in aPTT is noticed suddenly. It's only useful if tested in patients who complain of a bleeding tendency. Activated Partial Thromboplastin Time (APTT)
aPTT is a screening tool in coagulation disorders. It assesses intrinsic pathway of the coagulation cascade and elevated in vitamin K deficiency, hemophilias, vWF deficiency, liver diseases and other isolated coagulation factor deficiencies. In acquired type of coagulopathies the change in aPTT is noticed suddenly. It's only useful if tested in patients who complain of a bleeding tendency.
Von Willebrand Factor assays Abnormal vWF assay reports exclude vWF disease. Von Willebrand Factor assays
Abnormal vWF assay reports exclude vWF disease.
Coagulation factor assays Quantitative and qualitative assessment of factors (mainly VII, IX, XI) is the confirmation of diagnosis. Coagulation factor assays
Quantitative and qualitative assessment of factors (mainly VII, IX, XI) is the confirmation of diagnosis.
Assays for inhibiting factors There are various biochemical methods assessing inhibitors of coagulating factors. Quantitative assessment of them is important in management. Measured in Bethesda Units. Assays for inhibiting factors
There are various biochemical methods assessing inhibitors of coagulating factors. Quantitative assessment of them is important in management. Measured in Bethesda Units.
Lupus anticoagulant As an indicator of autoimmune disease. High titers are associated with bleeding and thrombosis. Lupus anticoagulant
As an indicator of autoimmune disease. High titers are associated with bleeding and thrombosis.

Management - Supportive

Fact Explanation
Control of bleeding. The first priority is to stop acute bleeding. Some cases might need surgical procedures, i.e. draining of hematomas, resection of the organ or a part of it, to arrest life threatening internal bleeding. Control of bleeding.
The first priority is to stop acute bleeding. Some cases might need surgical procedures, i.e. draining of hematomas, resection of the organ or a part of it, to arrest life threatening internal bleeding.
Observe vitals. The patients with acquired hemophilia bleed without relation to the serum level of inhibitors. So, continuous close monitoring of vitals is essential, like in any other major bleeds. Observe vitals.
The patients with acquired hemophilia bleed without relation to the serum level of inhibitors. So, continuous close monitoring of vitals is essential, like in any other major bleeds.
Manage concomitant diseases Most of the patients with acquired coagulopathy are older and secondary to some other disease. It's important to manage the patient as whole, giving them a holistic care. Manage concomitant diseases
Most of the patients with acquired coagulopathy are older and secondary to some other disease. It's important to manage the patient as whole, giving them a holistic care.
Physical resting The patients might bleed spontaneously and unpredictably, so it's important to keep the patients physically resting as much as possible. Physical resting
The patients might bleed spontaneously and unpredictably, so it's important to keep the patients physically resting as much as possible.

Management - Specific

Fact Explanation
Intravenous fresh frozen plasma Even though there are fatal adverse effects reported, in emergency setting fresh frozen plasma (FFP) is indicated in factor IX deficiency. Intravenous fresh frozen plasma
Even though there are fatal adverse effects reported, in emergency setting fresh frozen plasma (FFP) is indicated in factor IX deficiency.
Intravenous cryoprecipitate FFP has no or low factor VIII. In emergency setting when recombinant factor is pending, cryoprecipitate which is a rich medium in FVIII and other coagulation factors can be used. Intravenous cryoprecipitate
FFP has no or low factor VIII. In emergency setting when recombinant factor is pending, cryoprecipitate which is a rich medium in FVIII and other coagulation factors can be used.
Recombinant coagulation factors Recombinant factors as to the deficient factor in assays. the most commonly used factor is the first ever developed rFVIII. There are lesser reported adverse effects than giving plasma components. Recombinant coagulation factors
Recombinant factors as to the deficient factor in assays. the most commonly used factor is the first ever developed rFVIII. There are lesser reported adverse effects than giving plasma components.
Activated prothrombin complex concentrate It's a FVIII bypassing agent used to ensure that coagulation cascade completes when there are inhibitors present. There are reported good response to APCC alone or combinations with rFVIII. Activated prothrombin complex concentrate
It's a FVIII bypassing agent used to ensure that coagulation cascade completes when there are inhibitors present. There are reported good response to APCC alone or combinations with rFVIII.
Immunosuppression Since the presence of auto-antibodies to the coagulation factors is the pathology, immunosuppression has proved to be effective in eradicating inhibitors. The drugs that been used are steroids and cyclophosphamide, alone or combined. The recovery rate has been proved to be significant is studies. The prescribed time is 5 weeks. Steroid pulses, calcineurin inhibitors and ciclosporin has also proved to be beneficial. Immunosuppression
Since the presence of auto-antibodies to the coagulation factors is the pathology, immunosuppression has proved to be effective in eradicating inhibitors. The drugs that been used are steroids and cyclophosphamide, alone or combined. The recovery rate has been proved to be significant is studies. The prescribed time is 5 weeks. Steroid pulses, calcineurin inhibitors and ciclosporin has also proved to be beneficial.
Rituximab Rituximab is a monoclonal chimeric antibody to the CD20 antigen and has proved to be ebenficial in eradicating inhibitors, especially in those who do not respond to or tolerate first line treatment. Rituximab
Rituximab is a monoclonal chimeric antibody to the CD20 antigen and has proved to be ebenficial in eradicating inhibitors, especially in those who do not respond to or tolerate first line treatment.
Intravenous immunoglobulin therapy Used as the second line treatment modality in the patients who are critical and do not respond to conventional treatment. There have been fatal adverse effects reported. Intravenous immunoglobulin therapy
Used as the second line treatment modality in the patients who are critical and do not respond to conventional treatment. There have been fatal adverse effects reported.
Plasmapheresis Plasma exchange and immunoadsorption has removed inhibitors successfully but there have been reports of inhibitors in blood a couple of weeks later in some patients, so it's suggested to be combined with immunosuppression. Plasmapheresis
Plasma exchange and immunoadsorption has removed inhibitors successfully but there have been reports of inhibitors in blood a couple of weeks later in some patients, so it's suggested to be combined with immunosuppression.

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