Bleeding Disorders

General Presentation

• Many people complain of easy bruising.
• Few have an underlying blood disorder.

Key facts and checkpoints

• Purpura = petechiae + ecchymoses.
• Abnormal bleeding is basically the result of disorders of (1) the platelet, (2) the coagulation mechanism or (3) the blood vessel.
• There is no substitute for a good history in the assessment of bleeding disorders.
• The first step is an assessment of personal and family histories.
• When someone describes ‘bruising easily’ it is important to exclude thrombocytopenia due to bone marrow disease and clotting factor deficiencies such as haemophilia.
• The commonest cause of an acquired bleeding disorder is drug therapy (e.g. aspirin, NSAIDs, cytotoxics and oral anticoagulants).
• Bleeding secondary to platelet defects is usually spontaneous, associated with a petechial rash and occurs immediately after trauma or a cut wound.¹ The bleeding is usually mucosal (e.g. bleeding from gingiva, menorrhagia, epistaxis and petechiae).
• Bleeding caused by coagulation factor deficiency is usually traumatic and delayed (e.g. haemorrhage occurring 24 hours after a dental extraction in haemophilia).
• Laboratory assessment should be guided by the clinical impression.
• The routine screening tests for the investigation of a true bleeding disorder can occasionally be normal, even despite a severe haemorrhagic state. Second-line investigations will need to be undertaken.

Purpura

• Definition: Bleeding into the skin or mucous membranes, appearing as multiple small hemorrhages that do not blanch on pressure.
• Types:
  • Petechiae: Purpuric lesions 2 mm or less in diameter.
  • Ecchymoses: Larger purpuric lesions.

Bruises

• Large areas of bleeding resulting from subcutaneous bleeding.
• Abnormal bruising suggests a disturbance of hemostasis.
• Pathways arresting bleeding:
  • Vasoconstriction
  • Platelet plug formation
  • Activation of coagulation factors

Differential Diagnosis

• Palpable Purpura:
  • Due to underlying systemic vasculitis (e.g., polyarteritis nodosa).
  • Raised petechiae; finger palpation is important.
• Hemostatic Defect Causes:
  • Platelet disorders
  • Coagulation mechanism disorders
  • Blood vessel abnormalities
• Types of Bleeding
  • Platelet Defects: Spontaneous mucosal bleeding (e.g., gingiva, menorrhagia, epistaxis).Immediate bleeding after trauma.
  • Coagulation Factor Deficiency: Traumatic and delayed bleeding (e.g., 24 hours after dental extraction in hemophilia).
• Causes of Clinical Disorders
  • Coagulation Deficiencies: Reduction or inhibition of circulatory coagulation factors.
  • Platelet Abnormalities: Issues with platelet number or function.
  • Vascular Defects: Issues with vascular structure or endothelium.
• Classification of Bleeding Disorders
  • Primary Hemostatic Disorders:
    • Von Willebrand disease (vWD)
    • Thrombocytopenia
    • Platelet function disorders
  • Secondary Hemostatic Disorders:
    • Disorders of fibrin formation
    • Hemophilias

THE CLINICAL APPROACH

History Indicators of Systemic Bleeding Defect

• Spontaneous hemorrhage.
• Severe or recurrent hemorrhagic episodes.
• Bleeding from multiple sites (e.g., mouth, bladder, bowel).
• Bleeding out of proportion to trauma.
• Cutaneous bleeding.
• Gastrointestinal bleeding.
• Postpartum hemorrhage.
• Bleeding from tooth extraction/oral cavity.
• Menstrual history (e.g., menorrhagia).
• Muscle hematomas or hemarthrosis.
• Exclude local pathology contributing to blood loss (e.g., postoperative bleeding).

Diagnostic Tips

• Platelet Abnormalities:
  • Early bleeding following trauma.
• Coagulation Factor Deficiencies:
  • Delayed bleeding after initial hemostasis.
• Previous Coagulation Response:
  • Normal response to dental extraction, circumcision, or pregnancy indicates an acquired problem.
• MILD: Malignancy, Infection, Liver disease, Drugs.
• Second-Line Investigations:
  • Necessary if routine screening tests are normal despite a severe hemorrhagic state.

Family History

• Positive family history can indicate diagnosis:
  • Sex-Linked Recessive: Hemophilia A or B.
  • Autosomal Dominant: vWD, dysfibrinogenemias.
  • Autosomal Recessive: Deficiency of coagulation factors V, VII, X.
• Enquire about:
  • Blood in urine or stools.
  • Menorrhagia in women.
  • Size and frequency of bruises.
  • Return if new bruises appear.

Key Questions

• How long has the problem been apparent?
• Do you remember any bumps or falls causing the bruising?
• What sort of injuries cause you to bruise easily?
• Have you noticed bleeding from other areas (e.g., nose, gums)?
• Any rashes or blood blisters in the mouth?
• Family history of bruising or bleeding?
• General health?
• Any tiredness, weight loss, fever, or night sweats?
• Viral illness or sore throat beforehand?
• Alcohol consumption?
• Past reaction to tooth extraction?
• Painful swelling in joints?

Medication Record

• Obtain a complete drug history.
• Examples:
  • Vascular Purpura: Prednisolone, other steroids.
  • Thrombocytopenia: Cytotoxic drugs, carbamazepine, gold, sodium valproate, heparin, ranitidine, sulfonamides, quinine, quinidine, thiazide diuretics, penicillins, vancomycin, chloramphenicol.
  • Functional Platelet Abnormalities: Aspirin, other antiplatelet drugs, NSAIDs.
  • Coagulation Factor Deficiency: Warfarin, direct oral anticoagulants (e.g., dabigatran, rivaroxaban).

Examination and Investigations

Skin Examination

• Note bleeding nature and rash distribution.
• Look for hereditary telangiectasia, blood-filled vesicles, gum hypertrophy.
• Examine for signs of malignancy (e.g., sternal tenderness, lymphadenopathy, hepatosplenomegaly).
• Check ocular fundi for retinal hemorrhages.
• Urinalysis for blood (microscopic or macroscopic).

Initial Investigations

• Full blood count
• Platelet count
• blood film
• basic coagulation studies (PT, INR, aPTT).
• Further tests if coagulation defect suspected:
  • Fibrinogen level.
  • Thrombin time.
• If platelet pathology suspected:
  • Platelet count and blood film.
  • Platelet function analyzer (PFA-100).
• For inherited disorders:
  • Factor VIII, vW factor activity, vW factor antigen.

• Further Considerations:
  • ESR/CRP, blood group, autoimmune screening, kidney function tests, LFTs, serology for blood-borne infections, ferritin, plasma electrophoresis, skin biopsy.
  • Exclude pseudo-thrombocytopenia due to laboratory error or platelet clumping on a blood film and consider repeat collection.

Abnormal Bleeding in Children

Common Conditions

• Hemorrhagic Disease of the Newborn:
  • Self-limiting, usually presents on the second or third day of life due to vitamin K deficiency.
  • Routine prophylactic vitamin K has nearly eliminated this issue.
• Idiopathic Thrombocytopenic Purpura (ITP):
  • Common primary platelet disorder in children.
  • Acute and chronic forms with immunological basis.
  • Diagnosis: Peripheral blood film and platelet count.
  • Spontaneous remission within 4 to 6 weeks in acute ITP.
• Henoch–Schönlein Purpura (HSP):
  • DxT arthralgia + purpuric rash ± abdominal pain → Henoch–Schönlein purpura
    • IgA vasculitis affecting small vessels.
    • Commonest vasculitis of children.
    • All ages, mainly in children 2–8 years
    • Rash, mainly on buttocks and legs
    • Arthritis (in two-thirds): mainly ankles and knees
    • Abdominal pain—colicky (vasculitis of GIT)
    • Haematuria (in 90%): reflects nephritis
  • Classic triad:
    • Non-thrombocytopenic purpura
    • large joint arthritis
    • abdominal pain.
  • Diagnosis:
    • Clinical, based on characteristic rash distribution.
  • Associations
    • Kidney involvement—deposition of IgA immune complex (a serious complication)
    • Melaena
    • Intussusception
    • Scrotal involvement
  • Investigations
    • FBE (if abnormal platelets or white cells, consider alternative diagnosis)
    • Urine: protein and blood; spun specimen, micro for casts
  • Management
    • Largely symptomatic—analgesics
    • No specific therapy
    • Short course of steroids for abdominal pain (if intussusception excluded)
    • If haematuria: follow-up urine microscopy and kidney function especially if no resolution (in approximately 5%)

Infective States

• Severe infections (e.g., meningococcemia) can cause purpura due to angiitis and disseminated intravascular coagulation.

Abnormal Bleeding in Older Adults

• Senile Purpura: Atrophy of vascular supporting tissue.
• Steroid-Induced Purpura: Atrophy of vascular supporting tissue due to long-term steroid use.

Platelet Disorders

Features

• Petechiae, ecchymoses.
• Bleeding from mucous membranes.
• Platelet counts <50,000/mm³.

Immune (Idiopathic) Thrombocytopenic Purpura (ITP)

• Clinical Features:
  • DxT bruising + oral bleeding + epistaxis → ITP
  • Acute onset in children.
  • Easy bruising, petechiae.
  • Epistaxis, bleeding gums, menorrhagia.
  • No systemic illness, splenomegaly rare.
  • Isolated thrombocytopenia (platelets <20,000/mm³).
  • Normal physical examination.
  • Normal or increased megakaryocytes in bone marrow.

Types

• Acute Thrombocytopenia of Childhood:
  • Postviral reaction causing cross-reacting antibodies against platelets.
  • Risk of spontaneous hemorrhage, especially if platelet count <30,000/mm³.
  • Prognosis good, 90% resolve in 6 months.
• Chronic Idiopathic (Immune) Thrombocytopenic Purpura:
  • Relapsing illness, rarely undergoes spontaneous remission.
  • Treatment: Steroids, IV immunoglobulin, biological agents (e.g., rituximab).
  • Some may require splenectomy.

Thrombotic Thrombocytopenic Purpura

• Life-threatening syndrome of hemolytic anemia, thrombocytopenia, and high LDH.
• Clinical features: Fever, neurological and kidney abnormalities.
• Defect: Absence of a specific plasma protease.

Coagulation Disorders

Features

• Ecchymoses.
• Hemarthrosis and muscle hematomas.
• Usually traumatic and delayed.

Inherited Disorders

• von Willebrand disease
• haemophilia A
• haemophilia B

Acquired Disorders

• Disseminated Intravascular Coagulation (DIC):
  • Involves several anticoagulation factors

von Willebrand disease

• DxT menorrhagia + bruising + increased bleeding—1. incisions 2. dental 3. mucosal → vWD
• Autosomal dominant inheritance (common types)
• Equal sex incidence
• Classically presents with mucocutaneous bleeding
• Prolonged bleeding time
• Bleeding tendency exacerbated by aspirin
• Platelets normal (common types)
• Defective platelet adhesion at site of trauma combined with factor VIII deficiency⁷
• aPTT prolonged
• Positive vW factor antigen (low)
• vW factor ristocetin (low)
• vW factor collagen binding assay
• Menorrhagia and epistaxis common
• Haemarthroses rare

Haemophilia A

Clinical features

• Spontaneous haemarthroses, especially knees, ankles and elbows, are almost pathognomonic
• X-linked recessive pattern of inheritance
• Invariably only males affected (1 in 5000)
• Females theoretically affected if haemophiliac father and carrier mother
• The human factor gene has long been identified
• Severity levels:
  • – severe—bleed spontaneously
  • – moderate—bleed with mild trauma or surgery
  • – mild—bleed after major trauma or surgery
• Deficiency of factor VIII
• aPTT prolonged
• Normal prothrombin time and fibrinogen
• Many seropositive for HIV, hepatitis B or C (factor VIII concentrate transmission)
• Low platelet count should suspect HIV-associated ITP⁷
• DxT spontaneous haemarthrosis + muscle bleeds + delayed bleeding → haemophilia A
• Treatment
  • Infusion of recombinant factor VIII concentrates
  • Avoid aspirin

Haemophilia B (Christmas disease)

• Identical clinical features to haemophilia A

• Also an X-linked recessive hereditary disorder
• Incidence of 1 in 30 000
• Deficiency of coagulation factor IX
• Same laboratory findings as haemophilia A apart from specific factor assays
• Treatment is with recombinant factor IX concentrates

Management Principles for Abnormal Bleeding

• Diagnosis:
  • Stop or avoid drugs affecting hemostasis.
  • Control bleeding with appropriate drugs, blood products, and local measures.
  • Infuse appropriate blood components for coagulation factor deficiencies and platelet disorders.
• Referral:
  • Refer patients with identified defects to a consultant hematologist or hemophilia center.
  • Supervise planning for pregnancy, surgery, or dental extraction.

When to Refer

• Management not amenable to simple measures (e.g., local therapy, compression).
• Elective surgery or pregnancy planned.
• Platelet count <30,000/mm³.

Practice Tips

• Careful history and physical examination usually pinpoint the cause of the bleeding disorder.
• Drug therapy can unmask pre-existing hemostatic disorders.
• Consider DIC in acutely ill patients with abnormal bleeding.
• Be cautious of non-prescription therapies affecting oral anticoagulants or causing platelet dysfunction (e.g., Ginkgo biloba).