Blood 4 Flashcards
What are the major causes of bleeding?
- Trauma
- Surgery
- Vitamin K deficiency
- Genetic causes e.g. haemophilia
- Sepsis as it induces - Disseminated Intravascular Coagulation (DIC)
- Aneurysm rupture
Drugs
How does DIC lead to bleeding?
DIC is usually primarily caused by infection but can be caused by certain cancers. DIC means that many micro thrombi are produced throughout the body. Thrombi are produced due to intravascular tissue factor exposure - which is normally kept inside the cells of the endothelium until there is an injury to the blood vessel. The white blood cells secrete cytokines, telling the endothelial cells to express tissue factor. It is systemic - removing the essential localisation factor in coagulation. This means the coagulating factors are being used up at a rate faster than they can be produces. As a result, the individual is susceptible to bleeding due to reduced clotting factors.
What is AAA? How does it contribute to spontaneous bleeding?
Abdominal Aortic Aneurysm. An aneurysm is a weakening of a blood vessel wall, leading to progressive dilation of the vessel. An AAA occurs inferior to the renal artery and superior to the iliac artery. If the aneurysm ruptures, it can lead to a massive blood loss. The mortality rate is 50% once the aneurysm ruptures. It has a higher prevalence in men - and is more common in men over 60. Usually the presence of an AAA is asymptomatic.
How can Vitamin K induce bleeding?
Vitamin K is an important cofactor for an enzyme responsible for adding glutamic acid onto certain factors. As a result some coagulation factors are dependent on Vitamin K: these include Factor VI, Factor II, Factor IX and Factor X. A Vitamin K Deficiency therefore means these factors cannot be produced, and so thrombin is not produced. As a result fibrin is not produced and cannot consolidate the plug. This means that the primary plug is more unstable and suscepitible to breaking. Vitamin K needs to be obtained through the diet and so the disorder has mainly dietary causes. It is common in malnutrition, liver disease, newborns and alcoholics. It can be easily treated with a Vitamin K injection.
How does oral anticoagulation with Warfarin work?
Warfarin inhibits the enzyme Vitamin K expoxide reductase. This enzyme reactivates Vitamin K to be used as a cofactor. It is a competitive inhibitor and so its antidote is a Vitamin K injection.
It is commonly used to treat blood clots such as deep vein thrombosis and pulmonary embolism and to prevent stroke in people who have atrial fibrillation, valvular heart disease or artificial heart valves.
What are causes of acquired thrombocytopenia?
- Blood loss
- Leukaemia (Due to bone marrow failure)
- DIC
- Drug induced thrombocytopenia
- Immune Thrombocytopenia Pupura (ITP) - This as, for an unknown reason, some people produce antibodies against platelets. As a result, as soon as platelets are produced, they are destroyed.
What is the difference between Haemophilia A and Haemophilia B?
Haemophilia A is due to a defect in Factor VIII whereas Haemophilia B is due to a defect in Factor IX. Factor VIII and Factor IX form a complex of the surface of platelets - this complex is essential to activate Factor X. Without Factor X, Thrombin is not produced. Fibrin is therefore is not produced and the plug is not consolidated. Despite the difference in defects, both present similarly in clinical situations.
They will however need different injections (with the recombinant protein) to replace different factors.
What are the inheritance patterns of X-linked recessive disorders?
The gene is found on the leg of the X-chromosome that is missing in the Y chromosome. As a result, women tend to be carriers of the disorder as they have another X chromosome which can carry the normal gene. Men tend to be suffers to the disorder as they only have one copy of the gene.
The disease is therefore expressed phenotypically in men rather than women. Although differences in X chromosome inactivation can lead to varying degrees of clinical expression in carrier females since some cells will express one X allele and some will express the other. An example of this is Haemophilia.
What are the symptoms of Haemophilia?
- Joint bleeding (Constant bleeding can lead to inflammation of the joint, which can eventually result in stiff jaw. In this case, the individual is unable to move an arm or leg and so is dependent on others)
- Muscle bleeding
- Soft tissue
- life-threatening bleeding
How do we test for clotting disorders?
First identify the reason for the deficiency. To isolate the particular factor, mix the sample of the individual with normal plasma. If the blood clots, there is a deficiency in a factor. If the clot still doesn’t form, it suggests an inhibitor is present.
Then identify which part of the pathway, the defect is present in.
If present in the intrinsic pathway - an APTT (Activated Plasmin Thromboplastin Time) will show this. The time to clot will increase.
If present in the extrinsic pathway - a PT (Prothrombin test will show this). This test looks exclusively at Factor VII. Similarly, the time to clot will increase.
If present in the common pathway - a TT test will show this (Thrombin Time). Again the time to clot will increase.
If there is a factor deficient, use a process of elimination to find isolate the factor. This can be by adding one factor at a time, to see when the blood will clot.
What is Von Willebrand Factor?
Von Willebrand Factor is a protein that is used ion coagulation. It’s main roles include:
- Platelet adhesion
- Carries Factor VIII
How can Von Willebrand Factor deficiency result in disease?
A bleeding disorder called von Willebrand disease (VWD) occurs when VWF is deficient or qualitatively abnormal. This is as platelets cannot adheres to each other and aggregate and so a primary plug is not formed, leading to bleeding. It also means that carrying capacity of Factor VIII is reduced. This means the common pathway is impaired and the clots cannot be consolidated.
Describe the main types of Von Willebrand disease.
The factor is tested for using an ELISA:
Type 1 – the mildest and most common type. People with type 1 VWD have a reduced level of von Willebrand factor in their blood. Bleeding is mostly only a problem if they have surgery, injure themselves, or have a tooth removed.
Type 2 – in people with this type of VWD, von Willebrand factor doesn’t work properly. Bleeding tends to be more frequent and heavier than in type 1.
Type 3 – the most severe and rarest type. People with type 3 VWD have very low levels of von Willebrand factor, or none at all. Bleeding from the mouth, nose and gut is common, and joint and muscle bleeds can occur after an injury.
What are the main causes of spontaneous bleeding?
- Platelet disorders: Can be due to issues with platelet adhesion, Platelet-vessel wall interaction or defects in platelets granules, secretion and transduction.
- Decreased activity of blood clotting factors (for example, due to hemophilia, liver disorders, vitamin K deficiency, or the use of certain drugs)
- Defects in blood vessels e.g in senile purpora. The blood vessel walls weakens as we age.
- Use of drugs that inhibit clotting (anticoagulants), including heparin, warfarin, and direct oral anticoagulants
Liver disease (causing inadequate production of clotting factors)
What is the difference between minor and major bleeding?
Major bleeds require intervention:
plasma (e.g. to increase circulatory volume), platelets, coagulation factor concentrates
External Cause: trauma, surgery
Internal Internal: haemophilia (joint/muscle), aneurysm rupture, drug-induced, gastro-intestinal
Minor bleeds do not require treatment
e.g. normal bruises, menorrhagia (abnormally heavy bleeding at menstruation), epistaxis (nose bleed).
