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AnneMäkipernaa
TimeaSzanto

Assessment and Treatment of a Patient with Bleeding Diathesis

Essentials

  • In primary care, the principal aim should be to identify patients whose bleeding diathesis could be caused by leukaemia, meningococcal septicaemia or other acute systemic disease, severe haemorrhagic disease, medication-induced complication or an assault.
  • This article describes the assessment of a patient with a bleeding diathesis. The principles differ from those of the assessment of a patient with an acute haemorrhage.
  • Laboratory investigations are indicated in patients who have a bleeding diathesis either themselves or in their close relatives, or if there are laboratory findings suggesting a hereditary or acquired bleeding diathesis.
  • In addition to clinical examination, the patient's age, sex, underlying diseases, medication, and occurrence of bleedings in the patient and close relatives will provide essential information that is required before additional investigations are ordered.
  • A haemostatic disorder leading to a bleeding diathesis may be acquired or hereditary. In both cases, such a disorder may either be mediated via platelets or coagulation factors. Bleeding diathesis may also be caused by abnormal fibrinolysis or by structural abnormalities in the vessel walls or in connective tissue.

Diagnosis

  • The diagnosis of a bleeding diathesis is based on both careful clinical assessment and laboratory tests, including screening tests and special examinations.

History of bleeding

  • Is the bleeding abnormally profuse, prolonged, recurring or delayed?
  • Does the bleeding originate from a single or from several sites?
  • Is it possible to stop bleeding by applying pressure?
  • Is the bleeding spontaneous or induced by something (procedures, childbirth, trauma)?
  • Has the patient previously been in a situation where profuse bleeding was possible?
  • A specific questionnaire or checklist filled in together with the patient is helpful in directing the assessment of the bleeding diathesis. Find out about local availability.
  • A negative past history of bleeding is also of significance (problem-free tonsillectomy or normal recovery from accidents rule out the possibility of a severe hereditary haemorrhagic disease better than screening laboratory tests).
    • On the other hand, it may be possible, for example, that in mild von Willebrand disease (vWD) the physiological variation in the concentration of the vW factor, or its increase during pregnancy or with age, have protected the patient from bleeding in the past.
  • The following symptoms do not suggest a haemorrhagic disease: haemoptysis, haematemesis, blood in stools, melaena or subconjuctival bleeding Subconjunctival Haemorrhage (Suggillation).

Bleeding into the skin and mucous membranes

  • Caused by an abnormality of the blood vessels, or deficiency or functional disorder of platelets, and results in haematomas and bruising.
  • Signs suggestive of a haemorrhagic disease include
    • epistaxis (not associated with a cold; bleeding is prolonged, bilateral, frequently recurring and leads to anaemia)
    • bleeding from gums (after dental surgery, oozing or large clots continue on the day after the procedure)
    • heavy menstruation leading to anaemia since menarche
    • prolonged bleeding or (recurrent) delayed bleeding after tonsillectomy without a local cause
    • bleeding from the urinary or gastrointestinal tract without a local cause.
  • The most common cause of superficial bleeding is thrombocytopenia, but mild vWD or mild platelet function disorder are also rather common. A mild haemorrhagic disease may become manifest when the patient uses aspirin or other medication that interferes with the function of the platelets or e.g. omega-3 products.
  • Disturbances in the vascular wall or surrounding tissues are also possible:
    • advanced age, ”senile purpura”
    • hypertension, increased venous pressure
    • hereditary: Osler's disease (hereditary telangiectasia), Ehlers-Danlos syndrome
    • vasculitis: Henoch-Sch�nlein purpura, autoimmune diseases

Deep bleeding

  • Suggestive of coagulation factor deficiency
  • Typical findings:
    • deep and extensive bruising, tissue bleeding at several sites or spontaneous bleeding into the joints
    • delayed bleeding, i.e. bleeding will resume a few days after trauma or surgery.

Diagnostic guidelines according to the type and site of bleeding

Subconjunctival bleedingHypertension, thrombocytopenia, trauma (contact lens)
Haematomas (on the skin, mucous membrane)Thrombocytopenia
Papular bleeding in the lower legsCryoglobulinaemia, purpuras (Henoch-Sch�nlein)
Bleeding into the mucous membranesOsler's disease, von Willebrand disease, deficiency or functional disturbance of platelets
Bruising (extensive, deep)Deficiency of a single coagulation factor, trauma
Bruising (limited, superficial)Thrombocytopenia, von Willebrand disease, Cushing's disease
Bleeding into the jointsHaemophilia A and B, rarely some other coagulation factor deficiency

Investigations

  • A suspicion of a bleeding diathesis should be confirmed with laboratory tests. Laboratory tests may either be used for screening purposes or they may be specific.

Screening tests

  • Screening tests are not very sensitive and, therefore, clearly abnormal findings usually have some clinical significance.
  • However, screening tests may be normal in mild or rare severe haemorrhagic diseases (coagulation factor XIII deficiency, for example), and a special laboratory is needed to identify the aetiology of the condition.
  • Red cell and platelet count (isolated thrombocytopenia, see Thrombocytopenia.
  • Activated partial thromboplastin time (APTT)
    • A general indicator of the function of the intrinsic clotting mechanism (fibrinogen, prothrombin, F V, VIII, IX, X, XI and XII); does not measure F VII and XIII
    • Not very sensitive; the result will be abnormal only when, for example, F VIII or F IX are 30% lower than normal. It is therefore usually not of benefit in the diagnosis of mild vWD.
    • APTT will be prolonged if the sample contains any heparin and in the presence of a lupus anticoagulant, which does not cause a bleeding diathesis (nor does a deficiency of F XII cause bleeding).
  • Prothrombin time (INR)
    • A screening test used to evaluate the extrinsic clotting system. It measures the combined effect of F II, VII and X.
    • Abnormal results indicate vitamin K deficiency or warfarin therapy.
    • Prothrombin time under 40% (INR spontaneously over 1.5) is considered markedly abnormal.

Interpretation of blood coagulation screening tests in patients with a bleeding diathesis

Prothrombin time and APTT normalMild von Willebrand disease (F VIII normal)
F XIII deficiency
Functional disorder of platelets
APTT prolognedF V, X, II, VIII, IX, XI deficiency
F XII deficiency (> 180 s)
Lupus anticoagulant
(Direct anticoagulants, heparin therapy)
Prothrombin time lowVitamin K deficiency
Liver failure
F VII, X, II deficiency
(Warfarin, direct anticoagulants)
APTT prolonged and prothrombin time lowSevere liver failure
Severe DIC
Severe accumulation of anticoagulation therapy
Coagulopathy associated with massive blood transfusion
  • Reduced fibrinogen activity (less than 1 g/l) may lead to a bleeding diathesis, but concentrations with the potential to cause bleeding will not be detected by screening tests. Fibrinogen testing is useful also in the diagnosis of disseminated intravascular coagulation (DIC) in assessing the coagulation factor deficiency caused by an acute heavy bleeding.
  • If the platelet count and function are normal, the cause of the bleeding diathesis may be a coagulation factor deficiency. If APTT and INR are also normal, the patient is unlikely to have a coagulation factor deficiency. However, normal results do not rule out the possibility of a mild coagulation factor deficiency or F XIII deficiency.

Further investigations

  • Individual coagulation factor assays, bundled assays for investigation of bleeding diathesis or biochemical or functional platelet analyses carried out at specialist laboratories
    • if a screening test result was abnormal and an explanation is sought
    • if screening test results were normal but the patient has a bleeding diathesis.
  • If the platelet count, APTT and prothrombin time/INR are normal, but the patient has bleeding symptoms, the most common cause is von Willebrand disease (vWD), low von Willebrand factor (vWF) activity or vWD predisposition, or platelet dysfunction. Further investigations should include the test for vWF activity, vWF antigen, F VIII and possibly a platelet function assay with PFA (not from the initially sent sample) or a more extensive test package for investigation of a bleeding diathesis which, in addition to the vW tests, contains other coagulation factor tests..
  • If blood coagulation screening tests are abnormal and the platelet count and function are normal, bleeding diathesis may be caused by coagulation factor deficiency (see table 2).

Aetiology and treatment of a bleeding diathesis

  • A distinction must be made between replacement therapy in an acute haemorrhage and preparation of a patient with a bleeding diathesis for a medical or surgical procedure
  • Hereditary coagulation factor deficiencies Hereditary Coagulation Factor Deficiencies
  • Acquired bleeding diathesis associated with an underlying disease.
    • Prevention and treatment of bleeding should principally be aimed towards treating the underlying disease.
    • Liver disease: almost all coagulation factors are produced in the liver. Moreover, activated coagulation factors and fibrin degradation products are removed form circulation by the liver. Hepatic circulation is in direct connection with the spleen. Portal hypertension will hence result in blood congestion in the spleen, leading to reduced number of circulating blood cells, particularly platelets. Usually, bleeding diathesis will only become manifest in advanced live disease. The diagnosis of a coagulation disorder of a hepatic origin is based on prolonged APTT and an abnormal prothrombin time result.
      • The treatment of a coagulation disorder caused by a liver disease is supportive. Vitamin K is of no benefit, but the patient may benefit from the administration of clotting factor concentrate and platelets.
    • Kidney disease, uraemia
      • Symptoms consist of easy bruising and mucosal bleeding, principally due to platelet abnormality.
      • Dialysis and treatment of anaemia may improve the situation.
      • In a uraemic patient with a bleeding diathesis the possible need for aspirin should be evaluated separately.
    • Bleeding diathesis associated with infection
      • Bacteraemia is associated with thrombocytopenia which may be severe, particularly if platelet production is also impaired due to the underlying disease.
      • An infection may cause bleeding via vitamin K deficiency as broad spectrum antimicrobials prevent the function of intestinal microbial flora.
    • Blood diseases: leukaemias, thrombocytopenias and polycythaemias (see Acute Leukaemias in Adults Chronic Lymphocytic Leukaemia (CLL) Chronic Myelogenous Leukaemia (CML) Thrombocytopenia)
    • DIC (associated with infections, gestational complications, cancers)
    • In rare cases, specific autoantibodies may develop against coagulation factors.
      • Most commonly these autoantibodies target the coagulation factor VIII (”acquired haemophilia”). The clinical picture resembles that of haemophilia and the patient has spontaneous, extensive bleeds into the tissues. The condition is most common in elderly patients and there may be an underlying malignancy or an autoimmune disease.
      • An acquired von Willebrand disease may manifest as, in particular, intestinal bleeding diathesis. For example a lymphoproliferative or myeloproliferative disease may be behind such a condition.
    • Bleeding diathesis associated with medicine use
      • As a therapeutic effect: warfarin, heparin, thrombolytic agents, thrombocyte inhibitors, direct oral anticoagulants
      • As an adverse effect: aspirin (significant effect 3-5 days) and other anti-inflammatory drugs, drugs inducing thrombocytopenia and/or thrombocytic dysfunction (e.g. SSRI drugs, omega-3 products) Thrombocytopenia
      • A bleed caused by warfarin (see article Warfarin therapy Warfarin Therapy for details)
        • Should bleeding occur, warfarin treatment should be withdrawn.
        • If INR is higher than the therapeutic range but < 4.5 and there is no obvious bleeding, reduce the weekly dose by 10%.
        • If INR > 4.5 but < 9 with no obvious bleeding, suspend warfarin until INR is < 4.5 and continue with a dose that is reduced by 20%.
        • If the INR readings are as above and the risk of bleeding is high, 1-2.5 mg vitamin K should be given orally or intravenously. INR should be checked after 12-24 hours.
        • In case of serious bleeding or clear overdose, administer fresh frozen plasma and/or prothrombin concentrate and 5-10 mg of vitamin K intravenously.

    References

    • Hayward CPM. How I investigate for bleeding disorders. Int J Lab Hematol 2018;40 Suppl (1):6-14. [PubMed]
    • Boender J, Kruip MJ, Leebeek FW. A diagnostic approach to mild bleeding disorders. J Thromb Haemost 2016;14(8):1507-16. [PubMed]