Bibliographic Source(s)

• Finnish Medical Society Duodecim. Thrombocytopenia. In: EBM Guidelines. Evidence-Based Medicine [Internet]. Helsinki Finland: Wiley Interscience. John Wiley & Sons; 2007 Apr 27 [Various].

Guideline Status

This is the current release of the guideline.

This guideline updates a previous version: Finnish Medical Society Duodecim. Thrombocytopenia. In: EBM Guidelines. Evidence-Based Medicine [Internet]. Helsinki Finland: Wiley Interscience. John Wiley & Sons; 2005 Apr 17 [Various].

Guideline Category

Evaluation
Management
Treatment

Intended Users

Health Care Providers
Physicians

Guideline Objective(s)

Evidence-Based Medicine Guidelines collect summarize and update the core clinical knowledge essential in general practice. The guidelines also describe the scientific evidence underlying the given recommendations.

Target Population

Adults and children with thrombocytopenia

Interventions and Practices Considered

Evaluation

1. Assessment of causes of thrombocytopenia
2. Assessment of patient with and without symptoms
3. Laboratory studies as indicated such as haemoglobin leucocyte count and differential platelet count and bone marrow examination platelet antibody assessment
4. Manual check of platelets when a low count has been detected by automatic counter

Treatment/Management

1. Avoidance of or stopping possible thrombocytopenia-causing drugs
2. Monitoring of symptomless patients
3. Referral as indicated to a specialist (in internal medicine or haematology)
4. Hospitalization if symptoms of bleeding
5. Pharmacologic treatment of idiopathic thrombocytopenia (ITP) (corticosteroids including predniso[lo]ne; intravenous gamma globulin infusions; other drugs including immunosuppressants and fibrinolysis inhibitors)
6. Splenectomy
7. Transfusions

Major Outcomes Considered

• Incidence of drug-induced thrombocytopenia
• Need for platelet transfusion in chemotherapy-induced thrombocytopenia
• Platelet count and platelet recovery
• Adverse effects of treatment

Methods Used to Collect/Select Evidence

Hand-searches of Published Literature (Primary Sources)
Hand-searches of Published Literature (Secondary Sources)
Searches of Electronic Databases

Description of Methods used to Collect/Select the Evidence

The evidence reviewed was collected from the Cochrane database of systematic reviews and the Database of Abstracts of Reviews of Effectiveness (DARE). In addition the Cochrane Library and medical journals were searched specifically for original publications.

Number of Source Documents

Not stated

Methods Used to Assess the Quality and Strength of the Evidence

Weighting According to a Rating Scheme (Scheme Given)

Rating Scheme for the Strength of the Evidence

Levels of Evidence

1. Quality of Evidence: High

   Further research is very unlikely to change confidence in the estimate of effect

   • Several high-quality studies with consistent results
   • In special cases: one large high-quality multi-centre trial

2. Quality of Evidence: Moderate

   Further research is likely to have an important impact on confidence in the estimate of effect and may change the estimate.

   • One high-quality study
   • Several studies with some limitations

3. Quality of Evidence: Low

   Further research is very likely to have an important impact on confidence in the estimate of effect and is likely to change the estimate.

   • One or more studies with severe limitations

4. Quality of Evidence: Very Low

   Any estimate of effect is very uncertain.

   • Expert opinion
   • No direct research evidence
   • One or more studies with very severe limitations

Methods Used to Analyze the Evidence

Systematic Review

Description of the Methods Used to Analyze the Evidence

Not stated

Methods Used to Formulate the Recommendations

Not stated

Rating Scheme for the Strength of the Recommendations

Not applicable

Cost Analysis

A formal cost analysis was not performed and published cost analyses were not reviewed.

Method of Guideline Validation

Peer Review

Description of Method of Guideline Validation

Not stated

Major Recommendations

The levels of evidence [A-D] supporting the recommendations are defined at the end of the "Major Recommendations" field.

Clinical Approach

• Stop drugs possibly causing thrombocytopenia unless vitally indicated.
• If the thrombocytopenic patient has symptoms of bleeding immediate hospitalization is advisable.
• Remember the possibility of so-called pseudothrombocytopenia.

Basic Rules

• The pathophysiological mechanism of thrombocytopenia (blood platelet count <150 10⁹/L in late pregnancy <120 10⁹/L) may be
  • Decreased production in the bone marrow
  • Increased consumption
  • Increased sequestration in the spleen
• Artificially low platelet counts are occasionally obtained when counted from ethylenediaminetetraacetic acid (EDTA)-anticoagulated blood (pseudothrombocytopenia). When thrombocytopenia (<100 10⁹/L) is detected in a patient for the first time the same blood sample should be checked manually for the presence of thrombocyte aggregates.
• Thrombocytopenia is a symptom the cause of which should be clarified. Typical manifestations of thrombocytopenia are skin bruising and petechiae and mucous membrane bleeding. In particular gum and nasal bleeding is common. Bleeding may also take place in the gastrointestinal and urinary tracts. Menorrhagia is also common.
• A tendency towards bleeding is uncommon if the platelet count is 50 to 100 x 10⁹/L. Platelet concentrations of 10 to 50 x 10⁹/L are frequently associated with spontaneous bleeding and haemorrhages are often severe with platelet counts of <10 10⁹/L. Drugs that affect the platelet function (aspirin [ASA] clopidogrel) increase bleeding tendency already in a rather moderate thrombocytopenia.

Causes of Thrombocytopenia

Decreased Production

• Inborn causes
  • Inherited thrombocytopenias (rare)
  • Fanconi's anaemia
• Acquired causes
  • Aplastic anaemia
  • Bone marrow infiltrates (carcinoma leukaemia myelofibrosis myelodysplasia tuberculosis)
  • Ionizing radiation other causes of myelosuppression (cytotoxic chemotherapy)
  • Drugs (trimethoprim-sulfamethoxazole gold thiazide diuretics oestrogens interferons)
  • Deficiency of vitamins and other essential trace elements or nutrients (B₁₂ folate iron)
  • Viral infections
  • Heavy drinking
  • Pregnancy

Increased Consumption

• Inborn causes
  • Non-immunological (haemolytic disease of the newborn prematurity maternal pre-eclampsia infections)
  • Immunological alloimmune neonatal thrombocytopenia maternal idiopathic thrombocytopenia purpura (ITP)
• Acquired causes
  • Non-immunological (infections disseminated intravascular coagulation thrombotic thrombocytopenic purpura haemolytic-uraemic syndrome drug-induced over-consumption of platelets)
  • Immunological (drug-induced following blood transfusion chronic and acute ITP) (see the Finnish Medical Society Duodecim guideline: "Bruises and purpura in children: ITP and its differential diagnosis")

Platelet Sequestration

• Hypersplenism

Loss of Platelets

• Acute haemorrhage
• Haemoperfusion

Clinical Approach

Symptomless Patient Platelet Count 100–150 x 10⁹/L

• The general practitioner can safely follow the situation initially at intervals of a few months. If no underlying disease becomes evident and thrombocytopenia remains stable no further follow-up is required. All drugs causing thrombocytopenia should be avoided if possible. Alcohol consumption habits should be discussed.
• Many drugs cause thrombocytopenia relatively frequently (George et al. 1998) [C]. These include heparin quinidine chloroquine gold salicylates sulphonamides thiazides allopurinol phenytoin carbamazepine and trimethoprim.
  • Non-steroidal anti-inflammatory drugs (NSAIDs) (especially acetylsalicylic acid) and some other medicines (clopidogrel) frequently impair platelet function and bring about a bleeding tendency. This tendency is disproportionately strong among thrombocytopenic patients.
  • Paracetamol appears not to impair platelet function.

Symptomless Patient Platelet Count <100 10⁹/L

• Thrombocytopenia-causing drugs should be stopped. Basic investigations are performed: haemoglobin leucocyte count and differential platelet count and bone marrow examination.
• If the situation does not improve referral to a specialist in internal medicine or haematology is advisable.
• If there are no obvious reasons for thrombocytopenia platelet antibody assessment should be carried out early.

If a Thrombocytopenia Patient Has Symptoms of Bleeding

• He/she needs specialist care.
• It is important to detect the possible cause. Remember that the list of drugs possibly causing thrombocytopenia is very long. All these drugs should be avoided.

Idiopathic Thrombocytopenic Purpura (ITP)

• Treatment is planned by a specialist in internal medicine a paediatrician or haematologist.
• In adults predniso(lo)ne continues to be the first-line therapy. The starting dose is 1 to 2 mg/kg/day. Response to treatment is often achieved in 1 to 4 weeks. At least a partial response is observed in 70 to 90% of cases but a good one (i.e. platelet count >100 x 10⁹/L) in only 30 to 50% of the patients. After a maximal response is observed the drug is slowly (over weeks) tapered to the smallest dose resulting in an acceptable clinical situation say a platelet count >50 x 10⁹/L with no symptoms of bleeding. ITP in children is often a self-limited postinfectious condition (see the Finnish Medical Society Duodecim guideline: "Bruises and purpura in children: ITP and its differential diagnosis").
• Intravenous gammaglobulin infusions may induce a response faster than corticosteroids. Non-responders are treated with immunosuppressants or splenectomy.
• Fibrinolysis inhibitors may be used to reduce excessive mucous membrane haemorrhages such as nasal gastrointestinal and urinary tract bleeding and menorrhagia. Platelet transfusions are effective if no platelet antibodies are present. Massive bleeding is compensated with red cells fresh-frozen plasma and platelet concentrates.

Related Resources

Other Evidence Summaries

• Oprelvekin may accelerate platelet recovery and reduce the need for platelet transfusion in chemotherapy-induced thrombocytopenia (Wilde & Faulds 1998) [C].

Refer to the original guideline document for other Internet resources and related literature.

Definitions:

Levels of Evidence

1. Quality of Evidence: High

   Further research is very unlikely to change confidence in the estimate of effect

   • Several high-quality studies with consistent results
   • In special cases: one large high-quality multi-centre trial

2. Quality of Evidence: Moderate

   Further research is likely to have an important impact on confidence in the estimate of effect and may change the estimate.

   • One high-quality study
   • Several studies with some limitations

3. Quality of Evidence: Low

   Further research is very likely to have an important impact on confidence in the estimate of effect and is likely to change the estimate.

   • One or more studies with severe limitations

4. Quality of Evidence: Very Low

   Any estimate of effect is very uncertain.

   • Expert opinion
   • No direct research evidence
   • One or more studies with very severe limitations

Clinical Algorithm(s)

None provided

References Supporting the Recommendations

• George JN Raskob GE Shah SR Rizvi MA Hamilton SA Osborne S Vondracek T. Drug-induced thrombocytopenia: a systematic review of published case reports. Ann Intern Med 1998 Dec 1;129(11):886-90. [18 references] PubMed



• Wilde MI Faulds D. Oprelvekin: a review of its pharmacology and theraputic potential in chemotherapy-induced thrombocytopenia. Biodrugs 1998;10:159-71.

Type of Evidence supporting the Recommendations

Concise summaries of scientific evidence attached to the individual guidelines are the unique feature of the Evidence-Based Medicine Guidelines. The evidence summaries allow the clinician to judge how well-founded the treatment recommendations are. The type of supporting evidence is identified and graded for select recommendations (see the "Major Recommendations" field).

Potential Benefits

Effective evaluation and management of thrombocytopenia

Potential Harms

Artificially low platelet counts are occasionally obtained when counted from ethylenediaminetetraacetic acid (EDTA)-anticoagulated blood using automatic counters (pseudothrombocytopenia).

Description of Implementation Strategy

An implementation strategy was not provided.

IOM Care Need

Getting Better
Living with Illness

IOM Domain

Effectiveness

Bibliographic Source(s)

• Finnish Medical Society Duodecim. Thrombocytopenia. In: EBM Guidelines. Evidence-Based Medicine [Internet]. Helsinki Finland: Wiley Interscience. John Wiley & Sons; 2007 Apr 27 [Various].

Adaptation

Not applicable: The guideline was not adapted from another source.

Source(s) of Funding

Finnish Medical Society Duodecim

Guideline Committee

Editorial Team of EBM Guidelines

Composition of Group that Authored the Guideline

Primary Author: Esa Jantunen

Financial Disclosures/Conflicts of Interest

Not stated

Guideline Status

This is the current release of the guideline.

This guideline updates a previous version: Finnish Medical Society Duodecim. Thrombocytopenia. In: EBM Guidelines. Evidence-Based Medicine [Internet]. Helsinki Finland: Wiley Interscience. John Wiley & Sons; 2005 Apr 17 [Various].

Guideline Availability

This guideline is included in a CD-ROM titled "EBM Guidelines. Evidence-Based Medicine" available from Duodecim Medical Publications Ltd PO Box 713 00101 Helsinki Finland; e-mail: info@ebm-guidelines.com; Web site: www.ebm-guidelines.com.

Availability of Companion Documents

None available

Patient Resources

None available

NGC STATUS

This summary was completed by ECRI on December 17 2002. The information was verified by the guideline developer as of February 7 2003. The summary was updated by ECRI on April 2 2004 on October 5 2004 and June 28 2005. This summary was updated by ECRI on January 31 2006 following release of a public health advisory from the U.S. Food and Drug Administration regarding the use of WinRho SDF (Rho(D) Immune Globulin Intravenous [Human]). This NGC summary was updated by ECRI Institute on January 7 2008.

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This NGC summary is based on the original guideline which is subject to the guideline developer's copyright restrictions.

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