Definition: the propensity to develop thromboses due to a hereditary defect of clotting factors.
Classification / type of disease:
Epidemiology: typically 5-8% of popn have a thrombophilic state, but only addition of other risk factors will lead pt to suffer symptoms
Presenting symptoms / signs: DVT, PE, VTE, MI, CVA, portal vein thrombosis, renal vein thrombosis… symptoms will reflect each of these pathologies. May also p/c with purpura fulminans, skin necrosis, recurrent miscarriage, IUGR, stillbirth, pre-eclampsia…
Diagnostic investigations: FBC, PTT, TT, RT, fibrinogen tests, lupus anticoagulant, anti-cardiolipin Ab, anti-beta-2-glycoprotein-1-Ab, activated protein C resistance, factor V leiden, homocysteine levels.
Congenital: factor V Leiden, high homocysteine, SCA, antithrombin III def, protein C or S def, elevated factor VIII, plasminogen def, dysfibrinogenaemia.
Acquired: antiphospholipid Ab (cardiolipin, lupus), heparin induced thrombocytopaenia (HIT), paroxysmal nocturnal haemoglobulinuria, nephrotic syndrome, hyperestrogenaemia, HRT, myeloproliferative disorders, smoking, pregnancy, orthostatic hypercoagulability, cancers, obesity.
Treatment / management: no tx, unless severe – then long-term preventative anti-coagulants
Prognosis: depends on cause and its severity.
Other thrombophilic states = anti-phospholipid syndrome, economy class syndrome, prothrombotic neoplastic changes (trousseau’s syndrome), factor V Leiden.
“safest transfusion is one that is not given”
Blood groups: A, B, AB, O. Based on 3 allelic genes on chromosome 9. Autosomal dominant inheritance.
- Group O = no Ag, A&B – Ab. Freq in UK = 46%
- Group A = A – Ag, B – Ab, 42%
- Group B = B – Ag, A – Ab, 9%
- Group AB = A&B – Ag, no Ab, 3%
Rh group: need to know group for transfusions. 2 Rh genes chemically = RhD and RhCE
- Group O RhD-ve = no Ag therefore RBC universal donor, plasma has A&B – Ag therefore, universal plasma acceptor.
- Group AB Rh+ve = RBC universal recipient, universal plasma donor.
There are other blood groups besides ABO and Rh = Kell, Kidd, Duffy…..
Donation: self-deferral health questionaire, can do 3x yr (450ml / donation)
RBC last 35/7 at 4oC
Platelets last 5/7 at 20oC
FFP / Cryoprecipitate last for longterm.
Transfusion chain is meticulous, as is labelling of sample.
When to give???
- Indications = trauma, surgery, severe anaemia, thrombocytopaenia, haemophilia, SCA… but give what?
- Acute blood loss or lowering Hb through chronic cause = transfuse RBC
- BM failure = give platelets
- Coagulopathy / DIC = give FFP
A unit = up to 500mls
Addition of 1 x unit of RBCs = increase in Hb of 1 x gram.
Must have a Rh match for transfusion: Rh+ve can receive Rh+ve AND Rh-ve
Rh –ve can only receive Rh-ve
Infections which can be transmitted by transfusion =
- HIV-1 and HIV-2
- Human T-lymphotropic virus (HTLV-1 and HTLV-2)
- Hepatitis C
- Hepatitis B
- Treponema pallidum
- Chagas Disease
- variant Creutzfeldt-Jakob Disease
Other risks of transmission =
- Most common adverse reaction = febrile non-hemolytic transfusion reaction
- Bacterial infection and sepsis
- Viral infection = Hep B/C, HIV..
- Transfusion-associated acute lung injury (TRALI) = acute respiratory distress (fever, non-cardiogenic pulmonary oedema, hypotension).
- Volume overload
- Iron overload
- Anaphylaxis / immune mediated haemolysis
- A neutropaenia, with fever and systemic symptoms. If neutropaenia is severe, a bacteriaemia may also be present. Most commonly seen in CT pts who have myelosupression.
- Generally, patients with febrile neutropenia are treated with empirical antibiotics until the neutrophil count has recovered and the fever has abated; if the neutrophil count does not improve, treatment may need to continue for two weeks or occasionally more.
- Mild to low-risk cases = oral co-amoxiclav and ciprofloxacin
- More severe cases = cephalosporins or carbapenems
Haematology guideline values
RBC = 4.2-5.4 x 1012/L
Haemoglobin = 12-16g/dg
Haematocrit = normally 38% in women, 48% in men
Mean corpusclar volume (MCV) = 78-96 fL (<80 =microcytic, >100 =macrocytic)
Total WBC = 4.8×109 and 12×109/L
Neutrophils = 2.5-7.5 x 109/L
Platelets = 150-450 x 109/L
Reticulocytes = 0.8-2%
Bilirubin = 2-17µmol/L (raised in haemolysis of RBCs)
You should especially focus on the clinical aspects of the above diseases using the headings below as a guide:
a) Symptoms and presentations to be studied and/or discussed
Symptoms related to anaemia; symptoms related to thrombocytopenia; symptoms related to leucopenia, especially neutropenia; lymphadenopathy & splenomegaly; painful sickle crises; haemophilia related symptoms – joint bleeds, problems of surgical procedures. The myeloproliferative disorders. Revision of coagulation pathways.
b) Issues to be aware of; and common clinical problems to be seen and/ or discussed
Pyrexia of unknown origin (PUO) in the neutropenic patient; opportunistic infections of the lung; problems of chemotherapy; the hypercalcaemic patient; problems of central vein catheters; psychosocial support in haematologic malignancy; patients with haemoglobinopathy (especially sickle cell); fertility issues after chemotherapy and transplantation. Problems of blood clotting – both anticoagulation (warfarin/heparin) and procoagulant (thrombotic) disorders. The interpretation of the blood count in the anaemic patient.
c) Procedures to be done
Examination of lymph nodes & spleen; assessment of the patient with neutropenic fever; proper blood transfusion practice; assessment of a haemophilia patient with a bleed. Accessing blood results; from laboratory to ward computer.
d) Procedures to be seen
Venepuncture & venesection
Care of central (Hickman) lines
Bone marrow aspiration and trephine biopsy.
Likely pathologies to be examined =
Anaemia (Fe def)
Warfarin use/OD = how do you control INR?