What is the diagnosis and treatment for profound fatigue with easy bruising?

Profound Fatigue with Easy Bruising: Diagnosis and Management

The combination of profound fatigue and easy bruising requires immediate evaluation for hematologic disorders, particularly bone marrow failure syndromes like aplastic anemia, which presents with pancytopenia and can be life-threatening if untreated.

Immediate Diagnostic Priorities

Critical Laboratory Evaluation

• Obtain a complete blood count (CBC) with platelet count and peripheral blood smear immediately to assess for pancytopenia, which suggests bone marrow failure 1
• Check prothrombin time (PT) and activated partial thromboplastin time (aPTT) as initial coagulation screening 1
• Add fibrinogen level if PT or aPTT are abnormal to detect fibrinogen defects 1
• Assess for anemia-related fatigue, as hemoglobin levels directly correlate with fatigue severity and quality of life parameters 2

Key Historical Elements to Elicit

• Bleeding symptoms beyond bruising: significant bleeding after surgery or dental procedures, epistaxis, joint hemorrhages, or menorrhagia 1
• Medication review: document all anticoagulants, antiplatelets, NSAIDs, steroids, and alternative therapies that affect bleeding tendency 1
• Family history: specific bleeding disorders or ethnicity associated with higher rates of coagulation disorders 1
• Systemic symptoms: fever, weight loss, night sweats suggesting malignancy or infection 1

Physical Examination Focus

• Bruising pattern and location: bruising on buttocks, ears, or genitals has higher specificity for underlying pathology 1
• Signs of systemic illness: lymphadenopathy, hepatosplenomegaly, petechiae, pallor 1
• Connective tissue findings: hyperelastic skin, joint hypermobility suggesting Ehlers-Danlos syndrome 3

Differential Diagnosis Algorithm

Life-Threatening Conditions (Rule Out First)

• Aplastic anemia: presents with pancytopenia, profound fatigue, bruising, petechiae, and hypocellular bone marrow; requires urgent hematology referral 4
• Acute leukemia: pancytopenia with circulating blasts on peripheral smear 1
• Disseminated intravascular coagulation (DIC): consider in context of sepsis, trauma, or malignancy 1

Common Hematologic Causes

• Immune thrombocytopenia (ITP): isolated thrombocytopenia with easy bruising 5
• Von Willebrand disease (Type I): most common inherited bleeding disorder, but NOT reliably detected by PT/aPTT screening 1, 6
• Acquired hemophilia A: requires hematology consultation and may need corticosteroids, IVIG, or factor replacement 5
• Medication-induced: anticoagulants (warfarin, DOACs), antiplatelet agents, divalproex sodium requiring platelet monitoring every 6 months 5

Non-Hematologic Causes

• Ehlers-Danlos syndrome (vascular type): easy bruising from capillary fragility, normal coagulation studies except abnormal Hess test 3
• Vitamin K deficiency: prolonged PT, particularly in infants not given vitamin K at birth 1
• Chronic fatigue syndrome: debilitating fatigue with myalgias, tender lymph nodes, arthralgias, but without bruising as primary feature 7

Management Based on Findings

If Pancytopenia Identified

• Urgent bone marrow biopsy to evaluate cellularity and rule out infiltrative processes 4
• Immediate hematology referral for consideration of immunosuppressive therapy (antithymocyte globulin and cyclosporine) or stem cell transplantation 4
• Transfusion support: red cells for symptomatic anemia, platelets for counts <10,000 or active bleeding 4

If Isolated Thrombocytopenia

• Evaluate for anticoagulant use: consider reversal agents for major bleeding (4-factor PCC with vitamin K for warfarin, idarucizumab 5g IV for dabigatran, andexanet alfa for apixaban/rivaroxaban) 5
• Screen for immune checkpoint inhibitor therapy: may cause immune-related thrombocytopenia 5

If Suspected Von Willebrand Disease

• Specialized testing required: bleeding time, factor VIII coagulant activity, ristocetin cofactor activity, and von Willebrand factor antigen 6
• Desmopressin acetate (DDAVP): indicated for Type I von Willebrand disease with factor VIII levels >5%, administered 30 minutes prior to procedures 6
• Not effective for severe Type I or abnormal molecular forms of factor VIII antigen 6

If Normal Hematologic Workup

• Consider connective tissue disorders: particularly if joint hypermobility or skin hyperelasticity present 3
• Evaluate for chronic fatigue syndrome: if profound fatigue persists with myalgias, postexertional malaise, but normal laboratory studies 7
• Hematology referral still indicated when high clinical suspicion remains despite normal initial workup 1

Critical Pitfalls to Avoid

• Do not assume normal PT/aPTT excludes bleeding disorder: von Willebrand disease and factor XIII deficiency are not detected by these tests 1
• Do not overlook medication effects: certain drugs affect both bleeding tendency and coagulation test interpretation 1
• Do not delay bone marrow evaluation if pancytopenia is present, as aplastic anemia requires urgent treatment 4
• Do not perform extensive testing without clinical indication in patients with minor bruising and no other concerning features 1

When to Refer to Hematology

Immediate referral indicated for:

• Pancytopenia or unexplained cytopenias 4
• Abnormal initial coagulation studies 1
• High clinical suspicion despite normal screening tests 1
• Need for specialized testing (platelet function analyzer, von Willebrand studies) 1
• Suspected acquired hemophilia A or complex bleeding disorders 5