Easy bruising resident survival guide

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Sanjana Nethagani, M.B.B.S.[2]

Overview

Easy bruising is the bruising of skin with minor compression or pressure. When small capillaries of the superficial skin rupture from pressure or compression, petechiae occur, sometimes ecchymosis is also seen with insignificant trauma which is a bleed in the deeper layers in the skin. A wide variety of causes lead to easy bruising, some of which are clotting and bleeding disorders, platelet dysfunction, age related skin changes, and some forms of cancer such as leukemia.

Causes

Life threatening causes

• Thrombotic Thrombocytopenic Purpura
• Disseminated intravascular coagulation
• Leukemia
• Severe thrombocytopenia

Other causes

• Hemophilia A
• Hemophilia B
• Scurvy
• Von Willebrand disease
• Ehlers-Danlos syndrome
• Corticosteroid use
• Anticoagulant therapy
• Idiopathic Thrombocytopenic Purpura
• Henoch-Schonlein Purpura
• Vitamin K deficiency
• Liver disease
• Systemic Lupus Erythematosus
• Glanzmann Thrombasthenia
• Bernard-Soulier syndrome

For a full list of causes of easy bruising, click here.

Diagnosis

The algorithm below summarises approach to the different causes of easy bruising.

Detailed history: ❑ Is the bleeding over the limbs? ❑ Is there any bleeding in mucosal surfaces such as gums or oral mucosa? ❑ History of recent infections? ❑ Is there bleeding into the joints? ❑ Is there history of bruising after minor trauma in the past? ❑ Is there any associated rash? ❑ History of blood transfusions? ❑ History of bleeding after tooth extractions or surgeries ❑ Bleeding during menstrual cycle in women ❑ Drug history: Any use of the following in the past? Corticosteroids Heparin Warfarin Other anticoagulants Aspirin ❑ Family history of bleeding?

Characterize the symptoms ❑ Bruising with minor or no trauma ❑ Petechiae ❑ Gingival bleeding ❑ Menorrhagia ❑ Painful bleeding into joints

Initial investigations ❑ Complete blood count with platelet count ❑ PT/aPTT ❑ INR ❑ Liver function tests ❑ Thyroid function tests ❑ Renal function tests ❑ Peripheral smear ❑ Bleeding time ❑ Platelet function analyzer Other investigations ❑ Von Willebrand factor levels ❑ Factor VIII level ❑ Factor IX level ❑ Fibrinogen level ❑ ADAMTS13 level

Disorders of secondary hemostasis ❑ Abnormal PT/aPTT ❑ Abnormal factor assays ❑ Abnormal fibrinogen level

Decreased platelet count ❑ mild: 100,000 - 150,000 per µL ❑ moderate: 50,000 to 99,000 per µL ❑ severe: <50,000 per µL (may require transfusion)

Disorders of platelet function ❑ Prolonged bleeding time ❑ Thrombocytopenia ❑ Abnormal PFA-100 ❑ Abnormal Von Willebrand factor assay ❑ Abnormal Ristocetin induced platelet agglutination

Clotting factor disorders

Inherited

Acquired

❑ Von Willebrand disease * Abnormal Von Willebrand factor assay * Abnormal Glycoprotein 1b assay * Hypoactive agglutination on ristocetin induced platelet aggregation * Low factor VIII levels * Prolonged PTT ❑ Glanzmann's thrombasthenia * Abnormal platelet aggregation assays * Monoclonal antibody testing * Flow cytometry ❑ Bernard-Soulier syndrome * Giant platelets on peripheral smear * Abnormal ristocetin aggregation ❑ Oculocutaneous albinism/Hermansky-Pudlak syndrome * Absent dense bodies on electron microscopy of platelets * Abnormal platelet aggregation assays ❑ Chédiak-Higashi syndrome * Abnormal platelet aggregation assays * Defective platelet storage granules ❑ Isolated dense granule deficiency * Defective platelet aggregation * Decreased ADP/ATP ratio

❑ Uremia ❑ Acquired Von Willebrand disease ❑ Aspirin and other NSAIDs ❑ Glycoprotein IIb/IIIa inhibitors ❑ Cardiopulmonary bypass ❑ Dysproteinemia ❑ Myeloproliferative disorders ❑ Cardiopulmonary bypass ❑ Infections such as Dengue fever or Hepatitis C

Hemophilia A * Normal PT * Prolonged PTT * Abnormally low Factor VIII

Hemophilia B * Abnormally low Factor IX * Normal PT * Prolonged PTT

Hemophilia C * Prolonged aPTT * Abnormally low Factor XI

Low/undetectable fibrinogen * Afibrinogenemia * Hypofibrinogenemia * Hypodysfibrinogenemia

No abnormalities detected in initial analysis

❑ Consider other diagnoses ❑ Senile purpura ❑ Aplastic anemia ❑ Long term corticosteroid use ❑ Scurvy ❑ Vitamin K deficiency ❑ Domestic abuse ❑ Leukemia ❑ Meningococcal infection ❑ Ehlers-Danlos syndrome ❑ Alpha 2-antiplasmin deficiency ❑ Plasminogen activator inhibitor-1 deficiency ❑ Factor XIII deficiency ❑ Lupus anticoagulant ❑ Antiphospholipid syndrome ❑ ITP ❑ TTP/HUS ❑ Liver disease

Diagnostic clues

Shown below is a table summarizing different findings in easy bruising and their interpretation.

Platelet count	Bleeding time	RIPA	Peripheral smear	PT	aPTT	Fibrinogen	Thrombin time	Factor assays	Associated conditions
↓	↑	Normal	Few platelets on smear	Normal	Normal	Normal	Normal	Normal	Thrombocytopenia
Normal	↑	Hypoactive agglutination	Normal	Normal	Normal/ slightly prolonged	Normal	Normal	↓ Factor VIII	Von Willebrand disease
↓	↑	Hypoactive agglutination & normal ristocetin cofactor assay	Giant platelets	Normal	Normal	Normal	Normal	Normal	Bernard-Soulier syndrome
Normal	↑	Clumping with ristocetin	Normal	Normal	Normal	Normal	Normal	Normal	Glanzmann's thrombasthenia
Normal	Normal	Normal	Normal	Normal	↑	Normal	Normal	↓ Factor VIII, IX, XI or XII	Hemophilia A, Hemophilia B, use of Heparin, Antiphospholipid syndrome or Lupus anticoagulant
Normal	Normal	Normal	Normal	↑	Normal	Normal	Normal	↓ Factor VII	Factor VII deficiency, early in the course of treatment with warfarin, initial stages of liver disease
Normal	Normal	Normal	Normal	↑	↑	Normal	Normal	↓ Factor II, V & X	Factor II, V or X deficiency, oral anticoagulant use, Vitamin K deficiency, chronic liver disease
Normal	Normal	Normal	Normal	↑	↑	Normal	↑	Normal	Chronic liver disease, hyperfibrinolysis, heparin use
Normal/↓	↓	Normal	Normal	Normal	Normal	Normal	Normal	Normal	Splenomegaly, chemotherapy, immune mediated destruction
↓	↑	Normal	Normal	↑	↑	↓	↑	Normal	Multiple transfusions, massive blood loss
↓	↑	Normal	Shistocytes	↑	↑	↓	↑	Normal/↓	Disseminated intravascular coagulation

Management

The goal of treatment of easy bruising is to identify and treat the underlying disorder.

Categorize the bruises and other symptoms

Mild bruises

Moderate to severe bruises and other accompanying symptoms

❑ Rest ❑ Ice ❑ Elevation ❑ Compression ❑ NSAIDs for pain

Initial investigations Complete blood count with platelet count ❑ PT/aPTT ❑ INR ❑ Liver function tests ❑ Thyroid function tests ❑ Renal function tests ❑ Peripheral smear ❑ Bleeding time ❑ Platelet function analyzer

Thrombocytopenia Platelet transfusion after ruling out other conditions

Disorders of platelet function

von Willebrand disease ❑ Desmopressin releases weibel-palade bodies from endothelial cells ❑ von Willebrand factor concentrate ❑ Tranexamic acid ❑ Estrogen containing oral contraceptive pills for women who are affected ❑ Human-derived medium purity Factor VIII concentrate Glanzmann's thrombasthenia ❑ Avoid aspirin and NSAIDs ❑ Tranexamic acid or Aminocaproic acid ❑ Oral contraceptive pills to decrease menstrual bleeding ❑ Recombinant Factor VIIa Bernard-Soulier syndrome ❑ Platelet transfusion ❑ Tranexamic acid ❑ Avoid aspirin Acquired disorders of platelet function Uremic platelet dysfunction ❑ Erythropoietin can be used for prevention and treatment ❑ Cryoprecipitate can be used in bleeding diathesis ❑ Desmopressin is the agent used most commonly in active bleeding ❑ Estrogen acts by decreasing L-Arginine which in turn decreases Nitric Oxide which sees an increased production in uremia Drugs such as aspirin ❑ Discontinuation of drug ❑ DDAVP for mild bleeding ❑ Platelet transfusion for major bleeding Cardiopulmonary bypass ❑ Heparin ❑ Serine protease inhibitors such as aprotinin ❑ Decreasing platelet adhesiveness with Nitric oxide ❑ Dypyridamole Antiplatelet antibodies ❑ Corticosteroids ❑ Rituximab ❑ Splenectomy ❑ Intravenous immunoglobulin

Disorders of secondary hemostasis

Hemophilia A ❑ Recombinant Factor VIII ❑ Plasma transfusions ❑ Desmopressin for mild bleeds

Hemophilia B ❑ Factor IX infusion ❑ Blood or plasma transfusions in severe bleeding ❑ Avoid NSAIDs ❑ Tranexamic acid should be given before any procedure

Hemophilia C ❑ Fresh frozen plasma ❑ Recombinant Factor XI ❑ Cyclokapron is used as a preventative measure and treatment

Disorders of fibrinogen ❑ Afibrinogenemia and hypofibrinogenemia- plasma derived fibrinogen concentrate

No abnormalities detected on initial screen

Consider other diagnosis

Senile purpura ❑ Topical retinoids may be of some benefit

Infections ❑ Dengue fever * Oral rehydration therapy * Blood transfusion in severe cases ❑ Meningococcal infection * Third generation cephalosporins * Hydration

Aplastic anemia ❑ Bone marrow transplant ❑ Antithymocyte globulin ❑ Chemotherapy in some cases

TTP ❑ Transfusion is contraindicated ❑ Plasmapheresis ❑ Fresh frozen plasma ❑ Cryoprecipitate ❑ Corticosteroids ❑ Rituximab ❑ Caplacizumab ❑ Splenectomy ❑ Immunosupressive agents ITP ❑ Corticosteroids ❑ Splenectomy ❑ Intravenous immunoglobulin ❑ Romiplostim or Etrombopag HUS ❑ Hemodialysis ❑ Corticosteroids ❑ Plasmapheresis

Vitamin deficiencies ❑ Scurvy * Vitamin C supplementation ❑ Vitamin K deficiency * Phytonadione * Vitamin K by IV infusion for bleeding

❑Lupus anticoagulant * LMWH * Warfairn ❑ Antiphospholipid syndrome * Aspirin(preferred in pregnancy) *Warfarin * LMWH ❑ Ehlers-Danlos syndrome * There is no known cure * Physiotherapy and Occupational therapy Vitamin C may help with bruising ❑ Leukemia * Chemotherapy ❑ Plasminogen activator inhibitor-1 deficiency * Tranexamic acid * Aminocaproic acid ❑ Alpha-2 antiplasmin deficiency * Tranexamic acid * Aminocaproic acid ❑ Factor XIII deficiency * Factor XIII concentrate ❑ Liver disease * Eltrombopag * Romiplostim * Platelet transfusions if necessary ❑ Domestic abuse must be considered in any patient with multiple bruises after ruling out other pathologies

Do's

• Order a peripheral smear for all patients to rule out presence of shistocytes in conditions like TTP/HUS, DIC which need emergency treatment.
• Educate patients about red flag signs signs wherever appropriate such as epistaxis, hematemesis, melena, lethargy, pale and clammy hands and feet, oliguria or anuria.
• Early vaccination in all patients with hemophilia.
• Educate patients with bleeding disorders about wearing a medical identification tag in case of trauma or if emergency surgery is needed.
• Vitamin C and Vitamin K supplementation.
• Appropriate measures to increase factor levels or platelets before any dental procedures or surgeries such as factor infusion, cryoprecipitate, fresh frozen plasma, platelet or blood transfusions.