BLEEDING DISORDERS

By: Siti and Nurul

OBJECTIVES

1) Classify causes of bleeding disorders2) Clinical approach in making a diagnosis3) Review of certain bleeding conditions4) Discuss the current treatment strategies

BLEEDING DISORDER

S

Platelet disorder

Reduced count

Normal count

Coagulation factor disorder

Inherited

Acquired

CAUSES OF BLEEDING DISORDERS

PLATELET DISORDER

Reduced platelet count

Normal platelet count

Increased platelet

destruction or

consumption

Impaired platelet producti

on

Platelet dysfuncti

onVascular disorders

INCREASED PLATELET DESTRUCTION OR CONSUMPTION

Immune Immune thrombocytopenia purpuraSystemic lupus erythematosusAlloimmune neonatal thrombocytopenia

Non-immune

Haemolytic uremic syndromeDisseminated intravascular coagulationThrombotic thrombocytopenic purpuraCongenital heart dzGiant haemangiomas (Kasabach-Merritt syndrome)Hypersplenism

i) Platelet count reduced

Neonatal Alloimmune Thrombocytopenia  a disease that affects fetuses and newborns. Genetic differences between the fetus and mother may

result in the expression of certain antigens by fetal platelets, not expressed by the mother.

Fetomaternal transfusions result in the recognition of these antigens by the mother's immune system as non-self, with the subsequent generation of allo-reactive antibodies which cross the placenta.

NAIT, hence, is caused by transplacental passage of maternal platelet-specific alloantibody and rarely human leukocyte antigen (HLA) allo-antibodies (which are expressed by platelets) to fetuses whose platelets express the corresponding antigens.

Thrombotic thrombocytopenic purpura (TTP) a blood disorder that causes blood clots to form in small blood

vessels around the body and leads to a low platelet count D/t problems with a certain enzyme (ADAMTS13 aka von Willebrand

factor-cleaving protease) that involved in blood clotting cause clotting to occur in an abnormal way.

As the platelets clump together in these clots, fewer platelets are available in the blood in other parts of the body to help with clotting lead to bleeding under the skin and purpura.

In some cases, the disorder is inherited and patients are born with naturally low levels of this enzyme.

This condition also may be related to: Bone marrow transplantation Cancer Chemotherapy Hematopoietic stem cell transplantation HIV infection Hormone replacement therapy and estrogens Medications (including ticlopidine, clopidogrel, guinine,

and cyclosporine A)

Kasabach–Merritt syndrome (KMS) aka Hemangioma with thrombocytopenia is a rare disease, usually of infants, in which a vascular

tumor leads to decreased platelet counts and sometimes other bleeding problems which can be life-threatening

When these tumors are large or are growing rapidly, sometimes they can trap platelets, causing severe thrombocytopenia.

The combination of vascular tumor and consumptive thrombocytopenia defines KMS.

Tumors can be found in the trunk, upper and lower extremities, retroperitoneum, and in the cervical and facial areas.

This consumptive coagulopathy also uses up clotting factors, such as fibrinogen which may worsen bleeding DIC

Hemolytic anemia secondary to microangiopathic destruction (physical damage) of the RBCs can be expressed as mild, moderate, or severe

Hypersplenism an overactive spleen. The spleen helps filter old and damaged cells from

bloodstream. If it is overactive, it removes the blood cells too early and too quickly.

The spleen plays an important role in helping body fight infections.

Problems with the spleen can make one more likely to develop infections.

Causes:- Thalassemia Cirrhosis Lymphoma Malaria Tuberculosis Various connective tissue and inflammatory diseases

IMPAIRED PLATELET PRODUCTIONCongenital Fanconi Anaemia

Wiskott-Aldrich syndromeBernard-Soulier syndrome

Acquired Aplastic anaemiaMarrow infiltration e.g. leukaemiaDrug-induced

i) Platelet count reduced <con’t>

Aplastic anemia is a syndrome of bone marrow failure characterized

by peripheral pancytopenia and marrow hypoplasia. 

Fanconi anemia is the most common inherited form of aplastic

anemia due to an abnormal gene that damages cells, which

keeps them from repairing damaged DNA. To inherit Fanconi's anemia, a person must get one

copy of the abnormal gene from each parent (autosomal recessive)

The condition is usually diagnosed in children between 2 and 15 years old.

Wiskott-Aldrich syndrome (WAS) is a condition with variable expression, but

commonly includes immunoglobulin M (IgM) deficiency.

an X-linked recessive genetic condition; therefore, this disorder is found almost exclusively in boys. 

always causes persistent thrombocytopenia and, in its complete form, also causes:- small platelets, Atopy (eczema) cellular and humoral immunodeficiency increased risk of autoimmune disease and

hematologic malignancy.

Congenital platelet function defects Congenital platelet function defects are bleeding disorders

that cause reduced platelet function, even though there are normal platelet counts.

People with these disorders usually have a family history of a bleeding disorder that causes prolonged bleeding after minor cuts or surgery, or easy bruising.

Bernard-Soulier syndrome occurs when platelets lack a substance that sticks to the walls of blood vessels. This disorder may cause severe bleeding.

Glanzmann's thrombasthenia is a condition caused by the lack of a protein needed for platelets to clump together. This disorder may also cause severe bleeding.

Platelet storage pool disorder (aka platelet secretion disorder) is due to one of several defects that cause easy bleeding or bruising. It is caused by the faulty storage of substances inside platelets. These substances are usually released to help platelets function properly.

ii) Platelet count normalPLATELET DYSFUNCTION

Congenital Rare disorders e.g. Glanzmann thromboasthenia

Acquired UraemiaCardiopulmonary bypass

Uremia a clinical syndrome associated with fluid, electrolyte,

and hormone imbalances and metabolic abnormalities, which develop in parallel with deterioration of renal function.

Uremia more commonly develops with chronic renal failure (CRF) or the later stages of chronic kidney disease (CKD), but it also may occur with acute renal failure (ARF) if loss of renal function is rapid.

Toxins, such as parathyroid hormone (PTH), beta2 microglobulin, polyamines, advanced glycosylation end products, and other middle molecules, are thought to contribute to the clinical syndrome.

Severe complications of untreated uremia include seizure, coma, cardiac arrest and death.

Spontaneous bleeding can occur with severe uremia and may include gastrointestinal (GI) bleeding, spontaneous subdural hematomas, increased bleeding from any underlying disorder, or bleeding associated with trauma.

Cardiopulmonary bypass Over the past 2 decades, postoperative thrombocytopenia

a/w CABG has been brought to the attention of cardiac surgeons and hematologists because this complication is not uncommon and can seriously undermine the recovery of patients.

Among several causes of postoperative thrombocytopenia, heparin-induced thrombocytopenia with thrombosis (HITT) and thrombotic thrombocytopenic purpura (TTP) have been identified as 2 pathologic conditions that can result in high morbidity and mortality.

These complications are often associated with various life-threatening thrombotic syndromes and their diagnoses may be difficult at the onset of signs and symptoms.

Clinical presentations of these 2 diseases are almost identical, although their treatments should be different.

In both, thrombocytopenia occurs within a few days after CABG, and thrombotic syndromes (ie, gangrene of the toes and fingers) develop in association with progressive thrombocytopenia.

ii) Platelet count normal <con’t>

VASCULAR DISORDERSCongenital Rare disorders e.g. Ehlers-Danlos, Marfan

syndrome, hereditary haemorrhagic telangiectasia

Acquired Meningococcal & other severe infectionsVasculitis e.g. Henoch-Schonlein purpura, systemic lupus erythematosusScurvy

COAGULATION FACTOR DISORDER

INHERITED ACQUIREDHemophilia A and B Disseminated

intravascular coagulation

Von Willebrand disease

Liver disease

Other factor deficiencies

Vitamin K deficiency / warfarin overdose

CLINICAL APPROACH TO A BLEEDING CHILD

History Taking Age of onset (first episode?)

Neonate - in 20% of haemophilias, bleeding occurs in the neonatal period, usually with intracranial haemorrhage or bleeding after circumcision

Toddler - haemophilias may present when starting to walk

Adolescent - von Willebrand disease may present with menorrhagia

Location / pattern of bleeding

Muscle & joint : coagulation defect (characteristic of haemophillia)

Mucosa (gum, nose) & skin : epistaxis poorly controlled? Unilateral?

Scarring and delayed haemorrhage - suggestive of disorders of connective tissue, e.g. Marfan syndrome, osteogenesis imperfecta or factor XIII deficiency.

Type of bleeding Purpura, prolonged bleeding from superficial

cuts, epistaxis, GI bleeding, menorrhagia : platelet disorder, thrombocytopenia or von Willebrand dz

Precipitating cause If spontaneous: severe defect Crawling / walking? Cuts? Trauma? Surgery?

History Taking - rationale

Bruising and bleeding disproportionate to injury? Large or palpable bruising?

Frequency & duration of bleeding Quantify bleeding Associated symptoms

Infection –URTI Menorrhagia pad changes <2h, menses

>7days, >1 menstrual period/month Recent medications? NSAID (aspirin), cytotoxic,

anticoagulant (Heparin, Warfarin) Nutritional status? scurvy, decrease hepatic

synthesis

Medical hx (underlying dz) Presence of chronic dz e.g. liver / renal dz? Connective tissue dz e.g. Ehlers danlos

Surgical hx Dental extraction, tonsillectomy, circumcision

excess bleeding? Bleeding immediately after surgery indicate

defective platelet plug formation Bleeding after some hours indicate failure of platelet

plug stabilisation by fibrin dt coagulation defect

Family hx Detailed family tree required history of bleeding

disorder? Gender of affected relatives (if all boys, suggests

haemophilia)

1. Sex-linked recessive (hemophilia A, B)2. Autosomal recessive (clotting factors deficiency 2, 5,

7, 10, 11, 13)3. Autosomal dominant (von Willebrand, qualitative

platelet disorders)

Negative hx does not exclude a hereditary cause e.g. about 1/3 of hemophilia cases have negative family hx (mutations)

Petechiae-a small (1-2mm) red or purple spot on the body, caused by a minor hemorrhage (broken capillary blood vessels)

Purpura-red or purple discolorations on the skin that do not blanch on applying pressure-measure 3–10 mm-caused by bleeding underneath the skin

Petechiae and purpuraINFECTION

Meningococcemia

Group A strep

Atypical measles

Rocky mountain spotted fever

Echovirus 9, 4, 7

Epstein-Barr virus

Coxsackie virus A 9

NON-INFECTIOUSNormal platelets- Henoch Scholein

purpura- Coagulation disorders- Trauma

Low platelets- Immune

thrombocytopenic purpura

- Leukemia

Physical Examination General stability, vital signs Look for:

Anaemia: BM failure, leukemia Telangiectasia of lips: hereditary haemorrhagic

telangiectasia (HHT) Significant lymphadenopathy: leukemia, viral

(ITP) Stigmata of chronic liver dz: jaundice,

clubbing, palmar erythema, spider naevi

Detailed mucocutaneous exam Skin stigmata: petechiae, purpura, ecchymosis,

hematoma

Hepatosplenomegaly Musculoskeletal examination for bleeding and

extensibility Joint exam for range of motion and effusions If suspicious for non-accidental injury, assess for

child’s motor developmental milestones

1) PLATELET DISORDER

IMMUNE THROMBOCYTOPENIC

PURPURA (ITP)

What is thrombocytopenia ??

Platelet count less that 150 X 109 / L Lifespan of a platelet is 7 – 10 days & normal

count for all ages is 150 – 450 X 109 / L

Severity: 50 – 150 X 109 mild (low risk of bleeding) 20 – 50 X 109 moderate (bleed during op/

trauma) < 20 X 109 severe (risk of spontaneous

bleeding)

Definition of ITP Isolated thrombocytopenia with otherwise normal

blood counts in a patient with no clinical apparent alternate cause of thrombocytopenia e.g. HIV infection, SLE, lymphoproliferative disorders, alloimmune thrombocytopenia & congenital or hereditary thrombocytopenia

Pathogenesis Increased platelet destruction by

antiplatelet IgG autoantibodies In 80% of children, ITP is an acute, self-

limiting disorder (resolves spontaneously within 6-8 wks)

*Reduced platelet count compensatory increase of megakaryocytes in the bone marrow

Clinical Features Most child present between 2 – 10 yo Onset often acute Majority gave history of viral infection in

the preceding 2–4 wk Spectrum of bleeding

Cutaneous: petechiae, purpura Mucosal bleeds: gum bleeds & epistaxis Life threatening bleeds: intracranial

hemorrhage

Diagnosis Diagnosis of exclusion Based on history, physical examination, blood

counts, peripheral blood smear Physical examination: no lymphadenopathy or

hepatospenomegaly Blood counts: isolated thrombocytopenia, normal

Hb & white cell count Peripheral blood picture: normal apart from

reduced, larger platelets, no abnormal cells

Bone marrow aspiration is indicated: Atypical clinical features e.g. anaemia,

neutopenia, hepatosplenomegaly, marked lymphadenopathy exclude acute leukaemia or aplastic anaemia

Before starting steroid therapy avoid partially inducing an undiagnosed acute lymphoblastic leukaemia (ALL)

If there’s failure to respond to immunoglobulin therapy

When persistent thrombocytopenia > 6 months

Thrombocytopenia recurs after initial response to treatment

Other tests when there’s atypical presentationAntinuclear

factor and DNA

antibodies

Coomb’s test

CMV serology (those < 1

yo)

Coagulation profile

(non-accidental injury, inherited

bleeding disorder)

HIV testing (parents HIV +ve / IVDU)

Immunoglobulin levels (those with recurrent

infections)

Management Most can be managed at home & not require

admission Hospitalization if:

Platelet count < 20 X 109 / L with evidence of bleeding Platelet count < 20 X 109 / L without evidence of

bleeding but inaccessible to health care Parents request dt lack of confidence in homecare

Advices: Precautions with physical activities Avoid contact sports Immediately seek medical attention if bleeding occurs

Treatment is indicated when: Life threatening bleeding episode e.g. Intracranial

hemorrhage regardless platelet count Platelet count < 20 X 109 / L with mucosal bleeding Platelet count < 10 X 109 / L with any bleeding

Choice of treatment: Oral prednisolone 2 mg/kg/day X 2/52 then taper off Oral prednisolone 4 mg/kg/day X 4/7 IV immunoglobulin 0.8 mg/kg/dose for a single dose* IV anti-Rh(D)*Platelet transfusions are reserved for life-threatening hemorrhage as they raise the platelet count only for a few hours

Chronic ITP Persistent thrombocytopenia after 6

months of onset (occurs in 20%)

Wide spectrum of manifestations: Mild asymptomatic low platelet counts Intermittent relapsing symptomatic

thrombocytopenia Rare stubborn and persistent symptomatic

& hemorrhagic dz

Management Treatment is mainly supportive

Counseling & educate patient & caretakers regarding natural history of dz and how to detect problems and possible complications early

Drug treatment (second line therapies) only for chronic persistent bleeding that affects daily activities or impairs quality of life Pulses of steroids: oral Dexamethasone 1 mg/kg

given on 4 consecutive days every 4 weeks for 4 months

Intermittent anti Rh(D) immunoglobulin treatment for those who are Rh D +ve : 45-50 µg/kg. may cause drop in Hb levels

HAEMOLYTIC UREMIC

SYNDROME

What is HUS ?? characterized by progressive renal failure that is

associated with microangiopathic hemolytic anemia and thrombocytopenia.

most common cause of acute renal failure in children

Pathogenesis: the primary event is damage to endothelial cells

Cardinal lesion is composed of arteriolar and capillary microthrombi (thrombotic microangiopathy) and red blood cell fragmentation (schistocyte)

Clinical Features From history

prodrome of fever, bloody diarrhea (2-7 days before the onset of

renal failure) Irritability, lethargy Seizures Acute renal failure Oliguria / anuria

On examination, Pallor, often severe Hypertension Edema, fluid overload

Schistocyte -a fragmented part of a red blood cell (irregularly shaped, jagged and asymmetrical)

Treatment Meticulous attention to salt and water

balance Aggressive nutritional support e.g. total

parenteral nutrition Symptomatic

Tx of high blood pressure Tx seizure Kidney failure dialysis Anaemia blood transfusions Bleeding platelet transfusions

DISSEMINATED INTRAVASCULAR

COAGULATION (DIC)

SYSTEMIC ACTIVATIONOF COAGULATION PATHWAY

Thrombosis of smalland midsize vesselswith organ failure

Bleeding

Intravascular deposition of fibrin

in microvasculatureConsumption & depletion of

platelets and coagulation factors

Circulatory collapse e.g.

in meningococc

al septicaemia or extensive

tissue damage from

trauma or burns

Severe sepsis

Shock

Common clinical conditions associated with DIC

Obstetrical complicatio

nsAmniotic

fluid embolismAbruptio

placentae

Immunologic disorders

Severe allergic reaction

Transplant rejection

SepsisEscherichia

coliNisseria

meningitidis

Malaria

Vascular disorders

TraumaHead injury

Fat embolism

Reaction to toxin

Snake venomDrugs

MalignancyLung, prostate,

pancreatic

Features Predominant clinical features:

Bruising Purpura Hemorrhage

Pathophysiological process is characterised by microvascular thrombosis & purpura fulminants may occur

Diagnosis Microangiopathic haemolytic anaemia Thrombocytopenia Prolonged prothrombin time Prolonged activated partial thromboplastin

time Low fibrinogen Raised fibrinogen degradation products and D-

dimers Reduction in naturally occurring

anticoagulants, protein C and S and antithrombin

Schistocyte

Treatment approaches Treat underlying cause (usually sepsis) Tx complications (hypoxia, dehydration, acidosis, acute

renal failure)

If bleeding, replete coagulation factors Fresh frozen plasma 2 U (to replace clotting factors) Cryoprecipitate 10 U Platelet transfusion

If thrombosis, anticoagulation with IV heparin

2) COAGULATION FACTOR

DISORDER

Normal haemostasis Haemostasis describes the normal process

of blood clotting. It takes place via a series of tightly regulated interactions involving cellular and plasma factors.

There are five main components:i. Coagulation factors - are produced

(mainly by the liver) in an inactive form and are activated when coagulation is initiated (usually by tissue factor (TF), which is released by vessel injury;  

ii. Coagulation inhibitors - these either circulate in plasma or are bound to endothelium and are necessary to prevent widespread coagulation throughout the body once coagulation has been initiated

iii. Fibrinolysis - this process limits fibrin deposition at the site of injury due to activity of the key enzyme plasmin

iv. Platelets - are vital for haemostasis as they aggregate at sites of vessel injury to form the primary haemostatic plug which is then stabilised by fibrin

v. Blood vessels - both initiate and limit coagulation. Intact vascular endothelium secretes prostaglandin I2 and nitric oxide (which promote vasodilatation and inhibit platelet aggregation). Damaged endothelium releases TF and procoagulants (e.g. collagen and von Willebrand factor) and there are inhibitors of coagulation on the endothelial surface (thrombomodulin, antithrombin and protein S) to modulate coagulation.

Haemophilia

Table 22-3. Investigations in haemophilia A and von Willebrand disease

PT, prothrombin time; APTT, activated partial thromboplastin time; RiCoF, ristocetin co-factor, measures vWD activity.

Haemophilia A

von Willebrand

diseasePT Normal NormalAPTT ↑↑ ↑ or normalFactor VIII:C ↓↓ ↓ or normalvWF Antigen Normal ↓RiCoF (activity) Normal ↓Ristocetin-induced platelet aggregation

Normal Abnormal

vWF multimers Normal Variable

Severity of haemophilia

Factor VIII:C Severity

Bleeding tendency

<1% Severe Spontaneous joint/muscle bleeds

1-5% Moderate Bleed after minor trauma

>5-40% Mild Bleed after surgery

Definition A group of blood disorders in which there

is a defect in the clotting mechanism. Of X-linked recessive inheritance, but in

30% there is no family history as it is a spontaneous new mutation.

The most common haemophilias are: Haemophilia A – Deficiency of factor VIII

(85% cases) Haemophilia B – Deficiency of factor IX (15%

cases)

Clinical Manifestation

Bleeding in the neonatal period is unusual. Usually presents with easy bruising when

crawling and walking (9-12 months age). Haemarthrosis is characteristic of

haemophilia. Large joints are usually affected (knee, ankle, elbow); swollen, painful joints are common.

Epistaxis, gum bleeding, haematuria also occur.

Intracranial haemorrhages can be life threatening.

Bleeding may also occur spontaneously or after trauma, operation or dental procedures.

Severe arthropathy from recurrent joint bleeds in haemophilia. The aim of modern management is to prevent this from occurring.

Diagnostic Investigations

Full blood count Coagulation screen: PT, APTT Specific factor assay: FVIII level (low in

Haemophilia A) Specific factor assay: FIX level (low in

Haemophilia B) Bleeding time if applicable. Von Willebrand screen even if APTT normal.

Once a child is diagnosed to have haemophilia, check the viral status at diagnosis and then yearly. This is because treatment carries the risk of acquiring viruses. All haemophiliacs should be immunized against Hepatitis B.

Treatment 1) Prophylactic

Ideally, treatment of severe haemophilia should be to prevent arthropathy and ensure the best quality of life possible.

The dosage of prophylaxis is usually 25-35 U/kg of Factor VIII concentrate, given every other day or 3 times a week.

For Factor IX, the dosage is 40-60 U/kg, given every 2-3 days.

However, this form of management is costly and requires central venous access.

2) On demand treatment

clotting factors are inadequate.

replacing the missing factor Factor VIII

concentrates are used in haemophilia A,

Factor IX concentrates in Haemophilia BFresh frozen plasma and

cryoprecipitate ideally SHOULD NOT be used as there is a high risk of viral transmission.

Dose of factor required can also be calculated using the formulas below Units of Factor VIII: (% rise required) x (weight in kg) x

0.5. Units of Factor IX: (% rise required) x (weight in kg) x

1.4.

The percentage of factor aimed for depends on the type of bleed. For haemarthroses, 30-40 % is adequate. For soft tissue or muscle bleed aim for 40- 50 % level.

(there is potential to track and cause compression/ compartment syndrome) For intracranial bleeds or patients going for surgery,

aim for 100%.

Infuse Factor VIII by slow IV push at a rate not exceeding 100 units per minute in young children.

Factor VIII is given every 8 - 12 hours. Factor IX is given every 12 - 24 hours.

Duration of treatment depends on type of bleed: Haemarthroses 2-3 days. Soft tissue bleeds 4-5 days. Intracranial bleeds or surgery 7-10 days.

Veins must be handled with care. Never perform venous cut-down unless in an

emergency as it destroys the vein.

ComplicationsA. Joint destruction:

Recurrent haemarthroses into the same joint will eventually destroy the joint causing osteoarthritis and deformity.

This can be prevented by prompt and adequate factor replacement.

B. Acquisition of viruses Hepatitis B, C or HIV: immunisation and regular

screening recommended.

C. Inhibitors: These are antibodies directed against the exogenous

factor VIII or IX neutralizing the clotting activity. Overall incidence is 15-25% in haemophilia A and 1-

3% in haemophilia B. Can develop at any age but usually after 10 – 20

exposure days. It is suspected when there is lack of response to replacement therapy despite high doses.

Treatment requires “bypassing” the deficient clotting factor. Currently 2 agents are available - Recombinant activated Factor VII (rfVIIa or Novoseven) and FEIBA.

Immune tolerance induction is also another option. Management of inhibitors are difficult and requires

consultation with the haematologist in specialized centres.

Supportive Treatment Analgesia

There is rapid pain relief in haemarthroses once missing factor concentrate is infused.

If analgesia is required, avoid intramuscular injections.

Do not use aspirin or the non-steroidal anti-inflammatory drugs (NSAIDS) as they will affect platelet function.

Acetaminophen with or without opioids can provide adequate pain control.

Dental care Good dental hygiene is important as dental caries

are a regular source of bleeding. Dental clearance with factor replacement will be

required in severe cases.

Immunisations This is important and must be given: The

subcutaneous route is preferred. Give under factor cover if haematomas are

a problem.

SPECIFIC GUIDELINES FOR MANAGEMENT

1) Intracranial haemorrhage (ICH) Give factor replacement before suspected bleed is

confirmed by CT scan Aim to increase Factor VIII level to 100%.

For haemophilia B if monoclonal factor IX is used a level of 80% is adequate and if prothrombin complex concentrate (PCC) is used 50% level is recommended.

Urgent CT scan: If CT scan confirms ICH : maintain factor level 80%–

100% for 1–7 days and 50% for 8–21 days. If CT scan show no evidence of ICH, admit 1 day for

observation.

Follow up for long term sequelae. Lab investigations:

Pre-treatment factor assay level and inhibitor level before starting treatment and to repeat after 3 days of treatment to ensure adequate levels have been achieved and no inhibitor has developed.

Post treatment factor assay level ( ½ hour after infusion ) to ensure required factor level is achieved ( if the level is not achieved , consider development of inhibitors ) and should be repeated after 3 – 5 days.

follow up CT scan after 2 weeks

2. Surgery Pre-op investigations

• Full coagulation profile – PT, PTT • Pre-factor assay level and inhibitor level • Blood grouping, full antibody screening and full cross

matching if required. Calculate dose

½ hour before operation, infuse patient with appropriate factors.

Preferable level : 80-100% for factor VIII 70% for monoclonal factor IX 50% if prothrombin complex concentrate (PCC) used

Check post transfusion specific factor level ½ hour later if necessary or after surgery to ensure correct factor level is achieved.

Clotting factor level should be maintained above 50% during the operation

and 24 hours after surgery. Maintain adequate factor levels –

Days 1-3 60-80% 4-7 40-60% 8-14 30-50%

Repeat factor assay and check inhibitor level on day 3 to ensure adequate levels. Post operatively a minimum of 10 to 14 days replacement therapy is recommended.

3. Illiopsoas bleed Symptoms: Pain/discomfort in the lower abdomen/upper

thighs Signs: Hip flexed, internally-rotated, unable to extend Danger: Hypovolaemia, large volumes of blood may be

lost in the retroperitoneum. Management: Factor replacement: 50U/kg stat, followed by 25U/kg bd till

asymptomatic, then 20U /kg every other day for 10-14 days.

Ultrasound / CTscan to diagnose. Physiotherapy - when pain subsides. Repeat U/S to assess progress.

4. Haematuria

Bed rest. Hydration (1.5 x maintenance). Monitor for first 24 hours: UFEME & Urine C&S. If bleeding persists for > 24 hours, start factor

concentrate infusion. Perform KUB & Ultrasound of the kidneys. DO NOT give anti-fibrinolytic drugs (tranexamic

acid) because this may cause formation of clots in the tubules which may not recanalize.

5. Haemarthroses (Joint haemorrhages)

Most spontaneous haemarthroses respond to a single infusion of factor concentrate. Aim for a level of 30 % to 40%.

If swelling or spasm is present, treatment to level of 50% is required and infusion may have to be repeated at 12-24 hours interval until pain subsides.

Minor haemarthroses may not require immobilization, elastic bandage or slings and ice may help in pain relief.

Severe haemarthroses Splint in position of comfort. Rest. Early physiotherapy.

von Willebrand

disease (vWD)

Von Willebrand factor (vWF) has two major roles: It facilitates platelet adhesion to damaged endothelium It acts as the carrier protein for FVIII:C, protecting it

from inactivation and clearance.

quantitative or qualitative deficiency of von Willebrand factor (vWF).

This causes defective platelet plug formation and, since vWF is a carrier protein for FVIII:C, patients with vWD also are deficient in FVIII:C

autosomal dominant

Clinical features Bruising Excessive, prolonged bleeding after surgery Mucosal bleeding such as epistaxis and

menorrhagia.

In contrast to haemophilia, spontaneous soft tissue bleeding such as large haematomas and haemarthroses are uncommon.

Management Treatment depends on the type and severity of

the disorder Type 1 vWD -DDAVP,

secretion of both FVIII and vWF into plasma. used with caution in children <1 year of age as it can

cause hyponatraemia due to water retention and may cause seizures, particularly after repeated doses, and if fluid intake is not strictly regulated.

More severe types of vWD - plasma-derived FVIII concentrate

Intramuscular injections, aspirin and non-steroidal anti-inflammatory drugs should be avoided in all patients with vWD.

Vitamin K deficiency

Acquired disorders of coagulation

The main acquired disorders of coagulation affecting children are those secondary to: Haemorrhagic disease of the newborn due to vitamin

K deficiency

Liver disease

ITP (immune thrombocytopenia)

DIC (disseminated intravascular coagulation)

Vitamin K is essential for the production of active forms of factors II, VII, IX, X and for the production of naturally occurring anticoagulants such as proteins C and S.

Vitamin K deficiency therefore causes reduced levels of all of these factors.

The main clinical consequence of this is a prolonged prothrombin time and an increased risk of bleeding

This disorder can occur early, during the first week of life, or late, from 1 to 8 weeks of age.

Children may become deficient in vitamin K due to: Inadequate intake (e.g. neonates, long-

term chronic illness with poor intake)

Malabsorption (e.g. coeliac disease, cystic fibrosis, obstructive jaundice)

Vitamin K antagonists (e.g. warfarin).

Mild haemorrhage Bruising haematemesis Melaena prolonged bleeding of the umbilical stump

or after a circumcision. However, some suffer from intracranial

haemorrhage, half of whom are permanently disabled or die.

Prevention Intramuscular vitamin K on the 1st day of

life (0.5 to 1 mg)

Vitamin K should be given to all newborn infants to prevent haemorrhagic disease of the newborn.