Thrombophilia (and hypercoagulation)

21/10/2013 by admin | Haematology

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.

 

Aetiology: vast…

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.

 

Pathophysiology:

 

Transmission

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.

Blood transfusion

 

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

 

Special groups:

  • 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.

 

RBC:

 

O Rh-ve

 

 

A B

 

AB Rh+ve

 

Plasma:

 

O Rh-ve

 

 

A B

 

AB Rh+ve

 

 

 

 

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 =

 

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

 

 

Neutropaenic sepsis..

  • 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)

Lymphocytes??

 

 

 

 

 

 

 

 

 

 

 

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?

Neutropaenic sepsis

Leuakaemia

 

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