This lecture didn't come pre-packaged with learning outcomes (rather the Unit Guidebook has learning outcomes for the entire week, which isn't really helpful for this post) so I'm going to have to actually make up my own headings. Yaaaaaaaaayyyyyyyyyy.
Bleeding Disorders
Thrombocytopaenia
Thrombocytopaenia is a fancy word for "low platelet count." Usually we have around 150-400 * 10^9 platelets, but since we have a lot of redundancy, we usually don't show symptoms until platelets have dropped below 50 * 10^9 or so. When platelet levels are around 20-50 * 10^9, patients may bruise easily and bleed a lot following surgery. When platelet levels are 10-20 * 10^9, patients may have frequent nosebleeds and pinprick rashes called petechiae. If platelet levels are below 10 * 10^9, patients may experience serious bleeds. However, it is also important to note that low platelet count isn't always associated with increased bleeding. Sometimes platelets are low due to increased thrombosis throughout the body.
Thrombocytopaenia can be congenital, but is usually acquired. It may be acquired from certain drugs or from problems with the bone marrow that may arise during life (e.g. leukaemia). Hypersplenism can lead to thrombocytopaenia as the spleen stores platelets, so a larger spleen means that more platelets are stored and there are fewer circulating platelets. Another possible cause of thrombocytopaenia is Immune Thrombocytopaenic Purpura (ITP), an idiopathic condition in which there is increased destruction of platelets and inhibited megakaryocyte production (which in turn leads to reduced platelet production).
Platelet defects or deficiencies such as thrombocytopaenia usually lead to a pattern of bleeding called "mucocutaneous bleeding," in which petechiae are common but haematomas are not. There is usually immediate bleeding after procedures.
Haemophilia
Haemophilia is a congenital deficiency in clotting factors. In Haemophilia A, there is a deficiency of Factor VIII, whereas in haemophilia B, there is a deficiency of Factor IX. It is X-linked recessive, so it affects more males than females. Haemophilia can be diagnosed by looking at APTT (as both Factor VIII and Factor IX are in the intrinsic pathway, which is tested by APTT) and by directly measuring clotting factor concentrations. Haemophilia can be treated with recombinant FVIII or IX, which may be given routinely and/or prior to procedures. Most patients with haemophilia should have a card that contains useful details such as the severity and usual treatment.
Clotting factor deficiencies such as haemophilia usually lead to a pattern of bleeding called "deep tissue bleeding," in which haematomas are common (in cases of severe deficiency or following injury) but petechiae are not. There may be immediate bleeding after procedures, or it may be delayed.
Von-Willebrand's Disease
Von-Willebrand's Disease (vWD) is a deficiency of von-Willebrand Factor (vWF), which as discussed here is important for platelet adhesion to blood vessels. Therefore, vWD may present with the mucocutaneous bleeding seen in platelet deficiencies. vWF is also a carrier protein for factor VIII, so patients with vWD may also experience the deep tissue bleeding seen in clotting factor deficiencies. vWD is autosomal dominant, so it affects both sexes equally. It is also worse in people who are homozygous for the gene than in people who are heterozygotes.
There are three main types of vWD. In type 1 vWD, there is a decrease in quantity of vWF. In type 2 vWD, there is a decrease in function of vWF. Type 3 vWD is rare and is a severe deficiency of vWF seen in those who are homozygous for vWD. vWD can be diagnosed with a "von-Willebrand screen," which looks for vWF antigen, vWF function, and factor VIII levels.
Prior to procedures, patients with vWD can be given DDAVP (a.k.a. desmopressin), which releases any stored vWF in platelets and endothelium. The idea here is to maximise the amount of vWF present in the blood during the procedure. Tranexamic acid may be given for the first few days after the procedure in order to stabilise the fibrin clot. Patients who are severely vWF deficient or do not respond to DDAVP can be given biostate, which is essentially just Factor VIII and vWF from donor plasma.
Vitamin K Deficiency
Vitamin K deficiency is basically what it says on the box- a deficiency in vitamin K. As noted here, vitamin K is a cofactor in the carboxylation of clotting factor precursors, namely II (thrombin), VII, IX, and X. Deficiency in vitamin K leads to prolonged PT, either normal or prolonged APTT, and normal fibrinogen. Eat yo' leafy green veggies, kids (that's where a lot of dietary vitamin K comes from!).
Babies have very little vitamin K as it doesn't cross the placenta and there is very little in breast milk. Therefore, babies receive IM vitamin K at birth. (Unless, of course, they're born to extreme anti-vax parents who think that the vitamin K injection is a vaccine just because it's delivered by injection. Wonder what they think of the oral rotavirus vaccine.)
Liver Disease
As many clotting factors are made in the liver, liver disease leads to decreased production of clotting factors as well as decreased clearance of already-activated clotting factors. Liver disease also leads to decreased absorption of vitamin K. Therefore, many patients with liver disease will have increased PT and APTT, as well as decreased fibrinogen and platelets.
Massive Transfusion
"Massive transfusions" are transfusions of more than 50% of blood volume in 12-24 hours. This can be problematic as blood transfusions tend to be mostly packed cells and not much in the way of clotting factors and platelets. Over time, clotting factors and platelets may become diluted, leading to prolonged INR and APTT, as well as low fibrinogen and platelets. In order to combat the problems of massive transfusion, many institutions will make sure to transfuse some fresh frozen plasma in between transfusions of packed cells.
Disseminated Intravascular Coagulation (DIC)
In DIC, there is bleeding due to coagulation elsewhere in the body. In sepsis, severe trauma, and several other nasty conditions, there may be massive thrombin generation and widespread coagulation, which uses up clotting factors and platelets. Patients with DIC will have a severely prolonged INR and a severely prolonged APTT, as well as low fibrinogen and platelets. They may also have raised D-dimers (breakdown products of thrombi).
Thrombosis
Deep Vein Thrombosis (DVT)
Pulmonary Embolism (PE)
Sometimes blood clots, such as those seen in DVT, may break off and lodge elsewhere in the body. As venous clots travel through progressively larger veins before getting back to the right atrium, the first small veins that the clot will meet are usually in the lungs. A clot that has moved around the body is called an embolus, or a venous thromboembolism (VTE) if it came from the veins. A pulmonary embolism may cause chest pain and shortness of breath, so it has to be differentiated from other conditions that could cause these symptoms. Not all pulmonary emboli are symptomatic, but non-symptomatic PEs may have a fatal recurrence as the original blood clot may still be around and prone to breaking off again.
Factor V Leiden
Before I get onto talking about Factor V Leiden, I'm just going to give a quick mention to various anti-clotting mechanisms that our body has. Firstly, there is antithrombin, which can inhibit thrombin (duh) as well as some other agents of the clotting cascade (mainly IX, X, and XI). Secondly, there are proteins C and S, which are vitamin-K dependent and inactivate factors V and VIII.
Factor V Leiden, as you can probably guess by the name, affects Factor V. It is a point mutation that makes Factor V resistant to protein C, so that protein C can no longer inactivate it. Patients with Factor V Leiden are therefore more susceptible to blood clots and venous thromboemboli, but only around 5% of heterozygotes for Factor V Leiden will ever experience a VTE.
Prothrombin Gene Mutation
A prothrombin gene mutation is- you guessed it!- a mutation in the gene coding for prothrombin. Prothrombin is the precursor for thrombin. Prothrombin gene mutations tend to be gain-of-function, increasing the amount of prothrombin and the risk of thrombosis.
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