Chapter 39: Bruising and bleeding

Many patients present with the complaint that they bruise easily but only a minority turn out to have an underlying blood disorder. Purpura is bleeding into the skin or mucous membranes, appearing as multiple small haemorrhages that do not blanch on pressure. Smaller purpuric lesions that are 2 mm or less in diameter (pinhead size) are termed petechiae, while larger purpuric lesions are called ecchymoses (see FIG. 39.1).

Bruises are large areas of bleeding that are a result of subcutaneous bleeding. If bruising is abnormal and out of proportion to the offending trauma, then a disturbance of coagulation is suggested (see FIG. 39.2). The three spontaneous pathways that arrest bleeding following injury are vasoconstriction, platelet plugging of gaps and the coagulation cascade (intrinsic and extrinsic pathways).

‘Palpable purpura’ due to an underlying systemic vasculitis is an important differential problem. The petechiae are raised so finger palpation is important. The cause is an underlying vasculitis affecting small vessels (e.g. polyarteritis nodosa).

The decision to investigate is difficult because decisions have to be made about which patients warrant investigation and whether the haemostatic defect is due to local or systemic pathology.¹ The ability to identify a bleeding disorder is important because of implications for surgery, pregnancy, medication and genetic counselling.

The three major mechanisms of systemic bleeding disorders are (the Virchow triad):

1. coagulation deficiencies (reduction or inhibition of circulatory coagulation factors)

2. platelet abnormalities: of platelet number or function

3. vascular defects: of vascular endothelium

Bleeding disorders can also be divided into impaired primary or secondary haemostasis. Primary haemostatic disorders which are the most common include von Willebrand disease (vWD), thrombocytopenia and platelet function disorders. Examples of disorders of secondary haemostasis are disorders of fibrin formation and the haemophilias.²

A list of differential diagnoses of systemic bleeding disorders is presented in TABLE 39.1.¹

Differentiation of coagulation factor deficiencies and platelet disorders as the cause of a bleeding problem can usually be determined by a careful evaluation of the history and physical examination.

History

Factors that suggest the presence of a systemic bleeding defect include:

• spontaneous haemorrhage

• severe or recurrent haemorrhagic episodes, e.g. epistaxis

• bleeding from multiple sites

• bleeding out of proportion to the degree of trauma

• cutaneous bleeding

• gastrointestinal bleeding

• postpartum haemorrhage

• bleeding from tooth extraction/oral cavity

• menorrhagia

• muscle haematomas or haemarthrosis

If a bleeding diathesis is suspected it is essential to determine whether local pathology is contributing to the blood loss (e.g. postoperative bleeding, postpartum bleeding, gastrointestinal haemorrhage).

Diagnostic tips

• Platelet abnormalities present as early bleeding following trauma.

• Coagulation factor deficiencies present with delayed bleeding after initial haemostasis is achieved by normal platelets.

• A normal response to previous coagulation stresses (e.g. dental extraction, circumcision or pregnancy) indicates an acquired problem.

• If acquired, look for evidence of MILD: Malignancy, Infection, Liver disease, Drugs.

• A diagnostic strategy is outlined in TABLE 39.2.

Family history

A positive family history can be a positive pointer to the diagnosis:

• sex-linked recessive pattern: haemophilia A or B

• autosomal dominant pattern: vWD, dysfibrinogenaemias

• autosomal recessive pattern: deficiency of coagulation factors V, VII and X

Enquire whether the patient has noticed blood in the urine or stools and whether menorrhagia is present in women. A checklist for a bleeding history is presented in TABLE 39.3. The actual size and frequency of the bruises should be recorded where possible and if none are present at the time of the consultation the patient should return if any bruises reappear.

Key questions

• How long has the problem been apparent to you?

• Do you remember any bumps or falls that might have caused the bruising?

• What sort of injuries cause you to bruise easily?

• Have you noticed bleeding from other areas such as your nose or gums?

• Has anyone in your family had a history of bruising or bleeding?

• What is your general health like?

• Do you have any tiredness, weight loss, fever or night sweats?

• Did you notice a viral illness or sore throat beforehand?

• How much alcohol do you drink?

• What happened in the past when you had a tooth extracted?

• Have you ever had painful swelling in your joints?

Medication record

It is mandatory to obtain a complete drug history. Examples of drugs and their responses are:

• vascular purpura:

  • – prednisolone/other steroids

• thrombocytopenia:

  • – cytotoxic drugs

  • – carbamazepine

  • – gold

  • – sodium valproate

  • – heparin

  • – ranitidine

  • – sulphonamides

  • – quinine, quinidine

  • – thiazide diuretics

  • – penicillins, vancomycin

  • – chloramphenicol

• functional platelet abnormalities:

  • – aspirin

  • – NSAIDs

• coagulation factor deficiency:

  • – warfarin

Examination

Careful examination of the skin is important. Note the nature of the bleeding and the distribution of any rash, which is characteristic in Henoch–Schönlein purpura. Senile purpura in the elderly is usually seen over the dorsum of the hands, extensor surface of the forearms and the shins. Purpura on the legs indicates platelet disorders, meningococcal septicaemia and paraproteinaemias; on the fingers and toes indicates vasculitis.

Note the lips and oral mucosa for evidence of hereditary telangiectasia. Gum hypertrophy occurs in monocytic leukaemia. Search for evidence of malignancy, such as sternal tenderness, lymphadenopathy and splenomegaly. Examine the ocular fundi for evidence of retinal haemorrhages. Urinalysis, searching for blood (microscopic or macroscopic), is important.

Investigations

The initial choice of investigations depends upon the bleeding pattern.

If coagulation defect suspected:

• prothrombin time (PT), i.e. INR

• activated partial thromboplastin time (APTT)

• fibrinogen level

• thrombin time (TT)

If platelet pathology suspected:

• platelet count

• skin bleeding time (of doubtful value)

• platelet function analyser (PFA-100)

If inherited disorders suspected:

• factor VIII

• vW factor activity

• vW factor antigen

The full blood examination and blood film is useful in pinpointing the aetiology. Platelet morphology gives a diagnostic guide to inherited platelet disorders. The skin-bleeding time as a screening test of haemostasis has been shown recently to be severely limited by its lack of specificity and sensitivity and its routine use cannot be recommended. It is not a useful predictor of surgical risk of haemorrhage.^1,3 Other sophisticated tests, such as von Willebrand’s screen and platelet aggregation (e.g. PFA-100), can be advised by the consulting haematologist. One of considerable value is the bone marrow examination, which is useful to exclude the secondary causes of thrombocytopenia, such as leukaemia, other marrow infiltrations and aplastic anaemia.

Other tests to consider: ESR/CRP, autoimmune screening, kidney function tests, LFTs, plasma electrophoresis, skin biopsy. Be cautious of pseudo-thrombocytopenia due to laboratory error—exclude on a blood film and consider a repeat collection.

A summary of appropriate tests is presented in TABLE 39.4 and of blood changes for some coagulation factor deficiencies in TABLE 39.5.

Abnormal bleeding in children is not uncommon and once again the clinical history, particularly the past and family history, provides the most valuable information. It is important to keep non-accidental injury, such as child abuse, in mind in the child presenting with ‘easy bruising’. However, it is appropriate to exclude a bleeding disorder, especially a platelet disorder. Vigorous coughing or vomiting in a child can cause petechiae on or around the eyelids.

Coagulation disorders, including haemophilia and vWD, are usually suspected on clinical grounds because of widespread bruising or because of prolonged bleeding following procedures such as circumcision and tonsillectomy.

A common condition is haemorrhagic disease of the newborn, which is a self-limiting disease usually presenting on the second or third day of life because of a deficiency of coagulation factors dependent on vitamin K. The routine use of prophylactic vitamin K in the newborn infant has virtually eliminated this problem.

Idiopathic (immune) thrombocytopenic purpura (ITP) is the commonest of the primary platelet disorders in children. Both acute and chronic forms have an immunological basis. The diagnosis is based on the peripheral blood film and platelet count. The platelet count is commonly below 50 000/mm³ (50 × 10⁹/L). Spontaneous remission within 4 to 6 weeks occurs with acute ITP in childhood.³

The commonest vascular defects in childhood are:

• anaphylactoid (Henoch–Schönlein) purpura

• infective states

• nutritional deficiency (usually inadequate dietary vitamin C)

Henoch–Schönlein purpura

HSP, which is a type of IgA vasculitis, is the commonest vasculitis of children. It affects the small vessels, producing a leucocytoclastic vasculitis with a classic triad of non-thrombocytopenic purpura, large joint arthritis and abdominal pain. It is diagnosed clinically by the characteristic distribution of the rash (which is a palpable purpura) over the lower limbs, extending onto the buttocks (see FIG. 39.3), but it can also involve the upper limbs, trunk and even the face.

The onset of HSP typically follows an upper respiratory tract infection including a group A streptococcal tonsillopharyngitis.

The bleeding time, coagulation time and platelet counts are normal. The prognosis is good; most recover fully in a few months.

Clinical features

• All ages, mainly in children

• Rash, mainly on buttocks and legs (see FIG. 39.4)⁴

• Rash can occur on hands, arms and trunk

• Arthritis: mainly ankles and knees

• Abdominal pain—colicky (vasculitis of GIT)

• Haematuria (reflects nephritis)

Associations

• Kidney involvement—deposition of IgA immune complex (a serious complication)

• Melaena

• Intussusception

• Scrotal involvement

Investigations

• FBE

• 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

Infective states

The purpura associated with severe infections, such as meningococcaemia and other septicaemias, is due primarily to a severe angiitis. Disseminated intravascular coagulation usually follows.³

The outstanding causes are senile purpura and purpura due to steroids.⁵ The cause in both instances is atrophy of the vascular supporting tissue.

The features are:

• easy bruising and bleeding into skin

• ± mucous membrane bleeding

• investigations normal

Simple purpura (easy bruising syndrome)

This is a benign disorder occurring in otherwise healthy women usually in their 20s or 30s. The feature is bruising on the arms, leg and trunk with minor trauma. The patient may complain of heavy periods. Major challenges to the haemostatic mechanism, such as dental extraction, childbirth and surgery, have not been complicated by excessive blood loss.

Factitial purpura

Unexplained bruising or bleeding may represent self-inflicted abuse or abuse by others. In self-inflicted abuse, the bruising is commonly on the legs or areas within easy reach of the patient.

The features are:

• petechiae ± ecchymoses

• bleeding from mucous membranes

• platelet counts <50 000/mm³ (50 × 10⁹/L)

Immune (idiopathic) thrombocytopenic purpura

Clinical features⁵

• Acute onset in children

• Easy bruising and petechiae

• Epistaxis, bleeding gums and menorrhagia common

• No systemic illness

• Splenomegaly rare

• Isolated thrombocytopenia: platelets may be <20 000/mm³

• Other blood cells normal

• Otherwise normal physical examination

• Normal bone marrow with normal or increased megakaryocytes (acute leukaemia and aplastic anaemia should be excluded)

The two distinct types caused by immune destruction of the platelets are:

• acute thrombocytopenia of childhood—usually in children, usually postviral

• chronic ITP—autoimmune disorder, usually in adult women; all cases should be referred to a specialist unit

Acute thrombocytopenia of childhood

This is caused by a reaction to a virus infection resulting in the production of cross-reacting antibodies against platelets.

There is an early risk of spontaneous haemorrhage, so refer/admit to hospital especially if the platelet count is <30 × 10⁹/L or there is active bleeding.

The prognosis is good, invariably self-limiting—90% resolve in 6 months. It may recur with further viral infections. The rest pass into chronic ITP.

Bleeding is treated with immunoglobulin or steroids.

Chronic idiopathic (immune) thrombocytopenic purpura

Chronic ITP is a relapsing illness that rarely undergoes spontaneous remission and may require treatment with prednisolone or biological agents, e.g. rituximab. Ask about drug history. Some require splenectomy, but this operation is avoided where possible, especially in young children, because of the subsequent risk of severe infection, particularly with Streptococcus pneumoniae.⁵ (Refer later in this chapter.)

Thrombotic thrombocytopenic purpura

This is an uncommon life-threatening syndrome of haemolytic anaemia, thrombocytopenia and extremely high LDH. Clinical features include fever (non-infectious), neurologic and kidney abnormalities. The defect is in the absence of a specific protease in the plasma.

The features are:

• ecchymoses

• haemarthrosis and muscle haematomas

• usually traumatic and delayed

The inherited disorders such as haemophilia A and B are uncommon and involve deficiency of one factor only. The acquired disorders, such as disseminated intravascular coagulation (DIC), occur more commonly and invariably affect several anticoagulation factors (see TABLE 39.6).

Inherited coagulation disorders

A list of the inherited bleeding disorders is included in TABLE 39.1. The better-known disorders are vWD, haemophilia A and haemophilia B (Christmas disease).

von Willebrand disease

This is the most common disorder of haemostasis (incidence 1% of population) and is usually a mild problem with an excellent prognosis.⁶ There are about 22 types.

Clinical features

• Autosomal dominant inheritance (common types)

• Equal sex incidence

• Prolonged bleeding time

• Bleeding tendency exacerbated by aspirin

• Platelets normal

• Defective platelet adhesion at site of trauma combined with factor VIII deficiency⁶

• APTT prolonged

• Positive vW factor antigen

• Menorrhagia and epistaxis common

• Haemarthroses rare

Treatment

• No specific treatment

• Avoid aspirin (including Alka-Seltzer), NSAIDs, IM injections

• Be cautious of surgical and dental procedures

• Preparations that help include desmopressin acetate (DDAVP), factor VIII concentrates and tranexamic acid

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 ITP⁶

Treatment

• Infusion of recombinant factor VIII concentrates⁷

• 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

Main indications:

• immune thrombocytopenic purpura

• haemolytic anaemias esp. hereditary spherocytosis

• hypersplenism

• trauma

• Hodgkin/non-Hodgkin lymphoma

Post-splenectomy management⁸

Immediate problem is thrombocytosis (↑ platelets to 600–1000 × 10⁹/L) for 2–3 weeks with risk of thromboembolism.

Long-term risk is overwhelming infection (pneumococcus [especially] Haemophilus influenzae and meningococcus), especially in young children in the first 2 years post-splenectomy. For elective surgery give immunisation at least 2 weeks before surgery. Lifelong prophylaxis should be considered in select patients such as those severely immunocompromised.

Prophylaxis

• Education about risks and early recognition of infection (special care with malaria)

• Pneumococcal immunisation—give 2–3 weeks preoperative, repeat 5-yearly; avoid in pregnancy

• Haemophilus type B vaccine—once only if not immunised

• Meningococcus vaccine—every 5 years

• Influenza vaccine—annual

• Long-term penicillin: amoxycillin daily or phenoxymethylpenicillin bd

• Urgent hospital admission if infection develops

• Make the correct diagnosis.

• Stop or avoid drugs affecting the haemostatic system.

• Control bleeding episodes with appropriate drugs, blood products and local measures, such as simple compression or topical haemostatic agents.

• Infuse appropriate blood components for the treatment of coagulation factor deficiencies and some platelet disorders (e.g. factor VIII for haemophilia A, fresh frozen plasma for multiple factor deficiency).

• Refer patients with identified defects to a consultant haematologist or haemophilia centre.

• Supervise advanced planning in patients intending pregnancy, surgery or dental extraction.

• Management of haemorrhage is not amenable to simple measures such as local therapy with simple compression and other measures.

• Elective surgery or pregnancy is being planned.

• Platelet count <30 × 10⁹/L.

Post surgical management—splenectomy. Spleen Australia. Coagulation cascade. https://en.wikipedia.org/wiki/coagulation