- Von Willebrand disease is the most common inherited bleeding disorder, affecting an estimated 1 in 100 to 1 in 10,000 people. It is caused by deficiencies or defects in von Willebrand factor, which is important for platelet adhesion and stabilization of factor VIII. Common symptoms include easy bruising and mucocutaneous bleeding. Diagnosis involves screening tests like bleeding time, platelet count, prothrombin time, and activated partial thromboplastin time. Treatment depends on severity but may include desmopressin, antifibrinolytics, cryoprecipitate, or recombinant factor VIII.

1. POST-NEONATAL BLEEDING DISORDERS
09/02/2021
OBASOHAN. E.
DEPARTMENT OF PAEDIATRICS,
UCH, IBADAN.

2. OUTLINE:
• Introduction
• Epidemiology
• Hemostasis
• Classification
• Clinical features
• General Laboratory investigation
• Specific bleeding disorders
• Acquired bleeding disorders
• conclusion

3. INTRODUCTION
• Bleeding disorders refer to group of conditions marked by abnormal or excessive bleeding
and/or bruising.
• They are due to disorders of blood vessels, platelets or coagulation factors.
• They are sometimes referred to as clotting abnormalities or coagulopathies.
• Children are commonly brought to medical attention on account of excessive or
spontaneous bleeding or abnormal screening results from pre-surgical evaluation or a
known family history.
• They are in two main categories: hereditary or acquired.

4. EPIDEMIOLOGY
• According to The World Federation of Hemophilia (WFH):
- Bleeding disorders affects 1 in 1000 men and women globally
- There are proximately 315, 000 and 84, 000 persons living with hemophilia A and B
respectively.
• The three most common hereditary bleeding disorders are: Von Willebrand disease
(prevalence 1 in 100 – 1 in 10, 000), Hemophilia A and hemophilia B respectively.
• Nigeria:
• It is estimated that there are 9, 000 – 12, 000 people living with hemophilia in Nigeria
(Source: WFH)
• Majority of inherited bleeding disorder (estimate of 70%) remain undiagnosed and untreated.

5. EPIDEMIOLOGY CONTD
STUDY AUTHOR(S) SAMPLE
SIZE
KEY FINDINGS
Health Status of persons with
Hemophilia: A pilot survey from
a resource-constrained
country) from 36 persons with
hemophilia:
Year: 2019
Helen C. Okoye (UNTH),
Benedict Nwogoh (UBTH) and
Megan Adeniran (Haemophilia
Foundation of Nigeria, Kaduna)
36 Majority (88%) had access to
hemophilia treatment centre,
however with <6 consultations
in the past year
Only 11% had excellent health
status, 50% had good health
status and 38.9% had poor
health status
The Spectrum of inherited
bleeding disorders in pediatrics
Year: 2008.
Eman A El-Bostany et al
(Sausan Mubarek Hospital in
Cairo, Egypt and the King
Abdulaziz University Hospital,
Kingdom of Saudi Arabia)
43 27.9% of the children had VWD,
25.5% had hemophilia A
23.3% had bleeding with
undiagnosed cause
16.3% had platelet dysfunction
and 7% had hemophilia B.

6. HAEMOSTASIS
• The body possess innate mechanisms to control bleeding in the setting of injury (hemostasis)
• An understanding of this physiology process is critical in the identification and diagnosis of
bleeding disorders.
• The main components of the haemostatic process are the:
1. Vessel wall
2. Platelets
3. Coagulation proteins (coagulation factors)
4. Anticoagulant proteins
5. Fibrinolytic system

7. HAEMOSTASIS CONTD: SEQUENCE OF EVENTS
Platelet aggregation

8. HAEMOSTASIS CONTD.

9. BLOOD COAGULATION FACTORS

10. The picture depicts intrinsic (contact), extrinsic and common pathways of blood coagulation.

11. CLASSIFICATION / AETIOLOGY
VESSEL WALL ABNORMALITIES PLATELET DISORDERS COAGULATION DISORDERS
Congenital cause:
-Ehler’s-Danlos syndrome
-Hereditary haemorrhagic
telangiectasia
Acquired causes:
Henoch-Scholein purpura
Scurvy
Quantitative defects
-failure of megakaryocyte maturation,
-excessive platelet consumption: ITP, DIC, KMS
-Platelet sequestration: hypersplenism
Qualitative defects: Congenital
Glanzmann thrombasthenia
Bernard Soulier syndrome
VWD (Type 2B, platelet-type pseudo-VWD)
Wiskott Aldrich syndrome
Qualitative: acquired:
Myeloproliferative disorder, Drug-induced,
auto-antibody
Congenital:
Hemophilia
Von Willebrand disease -Type
2A
Acquired:
Liver disease
Vitamin K deficiency bleeding
DIC
Etc

12. CLINICAL PRESENTATION OF BLEEDING DISORDERS
VESSEL WALL
ABNORMALITIES
PLATELET DISORDERS COAGULATION
DISORDERS
Features:
1. mucocutaneous
bleeding, easy bruising
2. loose joints, lax skin,
Features:
mucocutaneous bleeding- petechiae,
ecchymoses, epistaxis, menorrhagia,
occasionally hematomas
Features:
deep bleeding into
muscles or joints
more extensive
ecchymoses and
hematoma formation

13. CLINICAL DIFFERENCES BETWEEN DISEASES OF VESSEL WALL/PLATELETS AND
COAGULATION FACTORS
PARAMETER PLATELET/VESSEL WALL
DISEASES
COAGULATION DISEASES
Mucosal bleeding Common Rare
Petechiae, purpura Common Rare
Deep haematomas Rare Characteristic
Bleeding from skin cuts Persistent Minimal
Sex of patients Equal >80% male

14. CLINICAL DIFFERENCES BETWEEN DISEASES OF VESSEL WALL/PLATELETS AND
COAGULATION FACTORS
ECCHYMOSES / BRUISE
PURPURA
PETECHIAE
Eyelid ecchymoses
Purpuric rash in 3 year
old child with
meningococcemia
Petechiae on the shin of
a patient with chronic
ITP.

15. SCREENING TESTS USED IN THE DIAGNOSIS OF COAGULATION DISORDERS
SCREENING TEST EXPLANATION REFERENCE CAUSE OF DERANGEMENT
Bleeding Time
(Two common
methods: Ivy
method, Duke
method)
a sharp-pointed object is used to
pierce the tip of the finger or lobe of
the ear. (it measures the time taken
for blood vessel constriction and
platelet plug formation to occur).
It assesses vascular integrity and
platelet
1-6 minutes (depends
largely on the depth of
the wound and the degree
of hyperemia in the finger
or ear lobe)
Platelet and vessel wall
disorders
Clotting Time Collect blood in a chemically clean
glass test tube and then to tip the
tube back and forth about every 30
seconds until the blood has clotted.
(it reflects the time taken for the
generation of thrombin)
It evaluates both the intrinsic and
common coagulation pathways.
6-10 minutes (varies
depending on method
used)
Coagulation factor
deficiency

16. SCREENING TESTS USED IN THE DIAGNOSIS OF COAGULATION DISORDERS
SCREENING TEST EXPLANATION REFERENCE CAUSE OF DERANGEMENT
Complete blood
count and peripheral
blood film
Details of various cells. The
platelet count is particularly
relevant here.
Platelet: 150-400 x 109/L Infection, platelet
disorders, etc
Prothrombin Time
(standardized with
INR)
To assess the extrinsic and
common pathway of
coagulation: VII, X, V, II,
fibrinogen
30-36 weeks: 10.6-16.2sec
Term infant: 10.1-15.9 sec
1-5 years: 10.6-11.4 sec
6-10 years: 10.1-12 sec
11-18 years: 10.2-12 sec
Liver disease,
Warfarin therapy
DIC
Activated Partial
thromboplastin time
It assesses the intrinsic
pathway.
30-36 weeks: 27.5-79.4 sec
Term infant: 31.3-54.3 sec
1-5 years: 24-36 sec
6-10 years: 26-36 sec
11-18 years: 26-37 sec
Haemophilia
DIC
Thrombin Time To assess the common pathway
(fibrinogen or inhibition of
thrombin by heparin)
11-16 sec DIC
Heparin therapy

17. OTHER SCREENING TEST OF HAEMOSTASIS
MIXING STUDY
A mixing study differentiates between
factor deficiencies and inhibitors.

18. ALGORITHM FOR INVESTIGATION OF ABNORMAL COAGULATION TESTS

19. TYPICAL COAGULATION PROFILES
DISEASE STATE PLATELET INR aPTT Fibrinogen D-dimer
Advanced liver
disease
↓ ↑ Normal or ↑ ↓ Normal or ↑
DIC ↓ Normal or ↑ Normal or ↑ Normal or ↓ ↑
VON
WILLEBRAND
DISEASE
Normal or ↓ Normal Normal or ↑ Normal Normal
HEMOPHILIA Normal Normal ↑ Normal Normal

20. PLATELET
H
• They play a critical role by:
I. forming the primary haemostatic
plug.
II. provide surface that concentrate
activated coagulation factors.
• Normal plate count range: 150-
400x109/L ; lifespan is 10 days.
• Thrombopoietin (TPO) is the major
regulator of platelet formation, 95%
is produced in the liver.
• One-third of marrow output are
trapped in the spleen ULTRASTRUCTURE OF PLATELET

21. The involvement of blood vessels, platelets and blood coagulation in haemostasis.

22. QUANTITATIVE PLATELET DISORDERS (THROMBOCYTOPENIAS)
DESTRUCTIVE IMPAIRED PLATELET PRODUCTION SEQUESTRATION
A. Immune thrombocytopenia
i. Acute idiopathic thrombocytopenia
ii. Chronic idiopathic thrombocytopenia
iii. Drug-induced (heparin-induced)
B. Non-immune thrombocytopenia
i. Thrombotic micro-angiopathic disorders
e.g HUS, TTP
ii. Thrombocytopenia of infections.
C. Combined platelet fibrinogen
consumption syndrome
Kasabach-Merrit syndrome,
DIC
A. Hereditary disorders
i. Congenital amegakaryotic
thrombocytopenia
ii. Thrombocytopenia-absent radius
(TAR) syndrome
iii. Wiskott Aldrich syndrome
iv. MY9-related thrombocytopenia:
(macrothrombocytopenias e.g.,
Sebastian, Epstein, May-Hegglin,
Fechtner).
B. Acquired disorders
i. Aplastic anemia
ii. Myelodysplastic syndrome
i. Hypersplenism
ii. Hypothermia

23. PLATELET FUNCTION DISORDERS
Congenital Acquired
A: Receptor defects
1. Bernard-Soulier syndrome
(deficiency of GP-1b,
macrothrombocytes)
2. Glanzmann thrombasthenia
(deficiency of GP IIB/IIIA receptor)
B: Dense body deficiency
1. Hermansky-Pudlak syndrome
2. Chediak-Higashi syndrome
C. Alpha-granule defects
1. Gray platelet syndrome
(macrothrombocytes)
2. Quebec platelet syndrome
1. Liver disease
2. Drug induced
i. NSAIDS
ii. Valproic acid
iii. High dose penicillin

24. APPROACH TO CHILDHOOD THROMBOCYTOPENIA

25. PLATELET TRANSFUSION
• One unit of random platelets (approximately 40 mL) per 10 kg will increase the platelet
count by 40 to 50 X 109/L if there is no:
1. active consumptive process (e.g., fever, immune thrombocytopenic purpura, sepsis,
alloimmunization, or DIC)
2. sequestration.
• This is equivalent to an increment in platelet count of 10 x 109/L per mL/kg of transfused
platelets (i.e., in a 10 kg child, 10 mL/kg or 100mL of transfused plates should raise the
platelet count by 100 x 109/L).

26. PLATELET TRANSFUSION Contd
• The platelet count should be checked 1 to 2 hours after infusion to identify refractory
patients.
• A patient is refractory if 1 hour after transfusion the platelet increment is less than 5 to 10 x
109/L per unit transfused for two separate transfusions.
• A patient is refractory if 1 hour after transfusion the platelet increment is less than 5 to 10 x
109/L per unit transfused for two separate transfusions.
• A patient may have platelet refractoriness secondary to alloantibodies (immune mediated).
• Nonimmune causes of platelet refractoriness are common and include splenomegaly, fever,
infection, DIC, and use of amphotericin B.

27. PLATELET TRANSFUSION Contd
• For refractory patients, a trial of cross-matched platelets should be given.
• Other possibilities for treatment should this fail include:
i. leukocyte-depleted,
ii. human leukocyte antigen (HLA)-matched platelets,
iii. intravenous immunoglobulin (IVIG) with HLA-matched platelets,
iv. or massive transfusion with random donor platelets (to overwhelm the antibody).
• Most institutions now utilize pheresed platelets that are harvested from a single donor
(250-350ml)

28. IDIOPATHIC THROMBOCYTOPENIC PURPURA(ITP)
• This is the most common cause of thrombocytopenia in the otherwise well child.
• The peak age is 1-4 years
• An autoimmune antibody IgG is formed against antigen on platelets membrane/surface.
• Antiplatelet antibody binds to complement, but platelets are not destroyed by direct
lysis.
• Destruction takes place in spleen, where splenic macrophages destroyes antibody
coated platelets.
• Severe bleeding is rare (<3% of cases)

29. IDIOPATHIC THROMBOCYTOPENIC PURPURA.
In Children(acute):
• Often precipitated by viral infectionand usually self limited
• Asymptomatic not febrile.
• Present with mucosal/skin bleeding, menorrhagia, purpura, petechiae
.
Adults(chronic: persistent thrombocytopenia for > 12 months):
• Commonly affects female.
• Ratio 2:1 (male/femaleratio)
• Peak incidence 20-50 years of age.
• Associated with HIV, H. pylori infection,

30. IDIOPATHIC THROMBOCYTOPENIC PURPURA
• Investigation
I. Severe thrombocytopenia (platelet count <20 × 109/L) is common
II. platelet size is normal or increased, reflective of increased platelet turnover
• Treatment:
I. Observation: for mild symptoms (petechiae and bruising)
II. Short course of prednisolone to raise platelet to > 20 000 x 109/L
III. Platelet transfusion, high dose corticosteroid and neurosurgery consult for intracranial
haemorrhage. Splenectomy for severe case unresponsive to medical therapy.
IV. Rituximab, thrombomimetics (romiplostim and eltrombopag), splenectomy, cytotoxic
drugs (Vincristine) for chronic ITP. Low dose Danazol may also be tried

31. VON-WILLEBRAND DISEASE
• FVIII is synthesized in the liver, kidney, etc. VWF is synthesized both in endothelial cells and
megakaryocytes, and stored in Weibel–Palade bodies and platelet α granules, respectively.
• Plasma vWF is majorly from endothelial cells. Stored vWF can be released by secretagogues
(desmopressin, adrenaline, stress).
• FVIII and vWF associate to form a complex in the circulation.
• Following endothelial injury, exposure of subendothelial vWF causes adhesion of platelets.
• Also the circulating vWF and vWF from released from the α-granules of platelets can bind
the exposed subendothelial, further contributing to platelet adhesion.
• The active form of vWF is in multimer.

32. VON-WILLEBRAND DISEASE
structure and function of factor VIII-von Willebrand factor complex.

33. VON-WILLEBRAND DISEASE
• This is the most common
inherited bleeding disorder
• Estimated prevalence:
1 in 100 – 1 in 10,000.
• Mode of inheritance
- Autosomal dorminant:
Majority of type 1, type 2
A, 2B and type 2M
- Autosomal recessive: type
2N, type 3 and some cases
of type 1 and 2A.
- New mutation in a few
case.
• Pathophysiology:
- Deficiency of VWF or failure
of multimerization or rapid
clearance or defect
- VWF is a carrier protein for
FVIII, protecting it from rapid
degradation.
Classification:
a. Quantitative defect:
Type1: mild-moderate
Type3: No detectable VWF
protein (the most severe)
b. Qualitative defect (type2)
• Clinical features:
- Typically presents with
mucosal bleeding as seen
with other platelet defect:
epistaxis, easy bruising
- Menorrhagia in women
- Type 3 can present like
hemophilia with joint
bleed. CNS haemorrhage
can occur.
- Type 2 is more severe than
type 1 because of lack of
VWF multimers assembly.

34. TYPES OF
VWD
SPECIFIC FEATURE DIAGNOSIS TREATMENT
Type 1
VWD:
(60-80% of
cases)
< VWF antigen
(VWF protein)
Type1c increased VWF
clearance
Low: 30 – 50 iu/dl
<30 iu/dl: likely
genetic
Desmopressin is
ineffective for type 1c
VWF-containing
concentrate
Antifibrinolytics (all
VWD)
TYPE 3 VWD: Most severe form
May present like hemophilia
with joint bleed.
CNS haemorrhage can occur
Absent VWF protein
Very low FVIII level
(≤10iu/dl)
Prophylaxis or modified
prophylaxis following
injury.
VWF-containing
concentrate

35. VON-WILLEBRAND DISEASE contd
TYPES OF VWD SPECIFIC FEATURE DIAGNOSIS TREATMENT
Type 2A VWD
(approx. 10% of
cases)
Defective VWF multimerization
resulting to reduced activity and
increased clearance. Loss of VWF
High Molecular weight multimers
(HMWM).
↓↓ VWF antigen
↓↓ VWF: RCo
Loss of HMWM
Desmopressin for minor
bleeding
Major bleeding require VWF
containing concentrate
Type 2B VWD Mutation in VWF resulting in
increased ability to bind platelet
Loss of VWF HMW
thrombocytopenia
↑Response to ristocetin
Desmopressin is relatively
contraindicated (accelerate
VWF binding and clearance)
Platelet-type
Pseudo-VWD
Mutation in GP1b receptor causing
spontaneous platelet binding
Loss of HMW Multimers
Thrombocytopenia
Platelet concentrate
Type 2M VWD Defect in ability of VWF to bind
platelet.
↓VWF antigen
↓VWF:RCo
Platelet and VWF concentrate
Type 2N VWD Inability of VWF to bind factor VIII.
Maybe misdiagnosed as
haemophilia
↓↓ FVIII. Normal or ↓
VWF antigen, VWF: Rco,
HMWM
Antifibrinolytics (for all VWD
with mucosal bleeding).

36. COAGULATION FACTOR DISORDERS
• Haemophilia A and B are among the
common and serious congenital bleeding
disorders
• Most coagulation factor disorders result
from reduced levels of these factors or
production of dysfunctional proteins.
• Coagulation factors are produced in the
liver. Platelets contain factor V.
• Source of factor VIII is still controversial:
said to be both hepatic (liver sinusoid
endothelial cells) and/or extrahepatic
(dendritic cells, endothelial cells).
• Factor VIII is bound to VWF in plasma to
prevent degradation (when bound, it is
inactive)
• Mode of inheritance:
1. X-linked: Factor VIII and IX deficiency
2. Autosomal recessive: Factor II, V, VII, XII XIII
3. Autosomal Dorminant: XI deficiency.
• Vitamin k dependent factors: II, VII, IX, X,
protein C and S.

37. HAEMOPHILIAS Incidence Pathophysiology
HAEMOPHILIA A
(Classical haemophilia,
Factor VIII deficiency)
Haemohilia B
(factor IX deficiency aka
Christmas disease)
1 in 5000 males.
A: 85% of cases
B: 10-15% of cases
X-linked.
Females are carriers but
may be affected if there
is Lyonisation of the
normal x-chromosome
Failure of activation of factor X.
(tenase) or factor X activating
complex is not formed).
30% of case of classical
hemophilia occur by new
mutation (so, no family history
in here).
Reduced clotting protein or
dysfunctional protein (B > A)
Haemophilia C
(Factor XI)
Rare.
More in Ashkenazi Jews.
Deficiency

38. HAEMOPHILIAS Clinical features
HAEMOPHILIA A (Classical
haemophilia
Factor VIII deficiency)
Haemohilia B
(factor IX deficiency
aka Christmas disease)
Depends on the severity FVIII activity
Mild: FVIII activity>5%. Asymptomatic, bleed with major trauma
Moderate: 1-5%. Mild trauma induce bleeding
Severe: <1% activity: Bleeding is often spontaneous.
Obvious symptoms: when the child starts to cruise
(intramuscular hematoma, hemarthroses-the hallmark).
(earliest joint affected is the ankle).
Repeated bleeding into one joint lead to development of target
joint.
Similar to haemophilia A
Haemophilia C (Factor XI) Bleeding is not as severe as above.

39. HAEMOPHILIAS Diagnosis Treatment
HAEMOPHILIA A (Classical
haemophilia
Factor VIII deficiency)
Haemohilia B
(factor IX deficiency)
Prolonged PTTK.
PT, platelet count,
bleeding time,
thrombin time are
normal.
Specific factor
assay
Bethesda assay for
inhibitors
For mild to moderate bleeding:
Desmopressin
Raise FVIII to haemostatic levels: 35-50%
For major or life-threatening
haemorrhage, aim for 100% activity
Live long prophylaxis for severe cases.
Desmopressin is ineffective.
Haemophilia C
(Factor XI)
Prolonged aPTT FFP. Aminocaproic acid / tranexamic acid
for minor bleeding.

40. Haemophilia A: HAEMARTHROSES WITH TARGET JOINT

41. COMPREHENSIVE CARE FOR HEMOPHILI A and B (MULTIDISCIPLINARY)
1.
PROPHYLAXIS
a. Recombinant replacement product: This is the standard of care for
most children with severe haemophilia.
- rFVIII concentrate (Hemophilia A): 20 – 40 IU/kg is given thrice weekly to
achieve trough level of >2% activity
- Primary prophylaxis (started at one year, prevents spontaneous bleeding
and joint deformity) is preferred to secondary prophylaxis (after having a
major bleed / target joint)
- Continuous replacement is preferred to intermittent prophylaxis
- Recombinant factors (<risk of infection) are preferred to plasma derived
factors
b. Anticipatory guidance: car seats, seatbelts, bike helmets, avoidance of
contact sports, avoid aspirin and other NSAIDS, Hepatitis B immunization.

42. COMPREHENSIVE CARE FOR HEMOPHILI A and B (MULTIDISCIPLINARY)
2.
Management
of bleeding.
- Desmopressin (for mild hemophilia A): transient increase in
FVIII level. (risk of hyponatremia )
- antifibrinolytics (tranexamic acid aminocaproic acid
especially for oral cavity bleed)
- rFVIII / rFIX.
- Prednisolone(added to rFVIII when hematuria is not
controlled)

43. COMPREHENSIVE CARE FOR HEMOPHILI A and B (MULTIDISCIPLINARY)
3. Management
of inhibitors
- These are antibodies that block the clotting activities in those who are
given FVIII or factor IX concentrate
- It is worse with Haemophilia A (25-25% of patients) compare to
haemophilia B (1-2%).
- Some patients loose the inhibitors with continuous infusion.
- Others: desensitization (immune tolerance induction), Rituximab,
activated prothrombin complex concentrate, emicizumab
4. Haemophilic
arthropathy.
Prevention is better with recombinant factor infusion.
synovectomy (radioisotope, open or arthroscopic)
5. Screening For HIV, Hepatitis B and C especially those receiving plasma derived factor
concentrate

44. STEPHEN CHRISTMAS
• He was two years old when he was taken to the
Hospital for Sick Children in Toronto, where his
bleeding history led to a diagnosis of hemophilia.
• As a baby, Stephen bruised easily. His first admission to
The Hospital for Sick Children (HSC) was at fourteen
months. Over the next four years, he had eight further
admissions.
• When a method to purify factor VIII as a
cryoprecipitate from human plasma was developed in
1965, it revolutionized hemophilia care.
• But by the early eighties the first hemophiliacs were
being diagnosed with AIDS. In 1985, at age 38 Stephen
tested positive for the human immunodeficiency virus.

45. ACQUIRED COAGULATION DISORDERS
1. Disseminated intravascular coagulation
2. Vitamin K deficiency bleeding
3. Liver disease

46. DISSEMINATED INTRAVASCULAR COAGULATION
• Definition:
- This is a thrombotic microangiopathy in which there is consumption of:
1. Clotting factors
2. Platelets
3. Anticoagulant proteins
- Any life-threatening severe systemic disease associated with hypoxia, acidosis, tissue
necrosis, shock, or endothelial damage may trigger DIC
- The key event: increased activity of thrombin that overwhelms its normal rate of removal.

47. DISSEMINATED INTRAVASCULAR COAGULATION
Entry of procoagulant
material into the
circulation
Widespread endothelial
damage
Other causes
1. Severe falciparum malaria
2. Severe tissue damage
3. Acute promyelocytic
leukemia
1. Gram negative septicemia
(e.g E. coli)
2. Meningococcemia
3. Viral infections: HIV, CMV,
varicella
Micro-angiopathic
disorders:
- Giant hemangioma
(KMS),
- HUS

48. DISSEMINATED INTRAVASCULAR COAGULATION
Inciting event
(life-threatening disease associated with hypoxia,
tissue necrosis, endothelial damage)
Activation and release of cytokines and
chemokines
Alteration of endothelium to prothrombotic state
HAEMORRHAGE
THROMBOSES
Consumption of
procoagulants
Consumption of
anticoagulants

49. DISSEMINATED INTRAVASCULAR COAGULATION
Confluent purpura in DIC
• Clinical features
- The main clinical presentation
is with bleeding
- Bleeding: usually first at venipuncture sites
or sites of surgical incision
- 5–10% of patients manifest thrombotic
lesions (e.g. with gangrene of limbs).
- microangiopathic haemolytic anemia

50. DISSEMINATED INTRAVASCULAR COAGULATION
• Investiagtions:
- Prolonged PT and PTTK.
- Low platelet
- Low fibrinogen
- Elevated fibrin degradation product
(e.g D-dimer) in serum and urine
- Blood film examination: the red cells
show prominent fragmentations
(damage sustained when passing
through fibrin strands in small vessels)
• Treatment
- Platelet concentrate
- Cryoprecipitate or fibrinogen
concentrate: hypofibrinogenemia
- FFP
- Red blood cell transfusion
- Heparin: for vascular thrombosis /
prophylaxis in high risk group.
- Treat the underlying cause.

51. VITAMIN K DEFICIENCY BLEEDING
• Fat‐soluble vitamin K is obtained from green vegetables and bacterial synthesis in the gut.
• Deficiency may present in the newborn (haemorrhagic disease of the newborn) or in later
life. (EARLY 0-24 hours, CLASSIC 2-7 days and LATE ONSET 1-6 MONTHS)
• vitamin K facilitates posttranscriptional carboxylation of factors II, VII, IX, and X. In the
absence of carboxylation, PIVKA (proteins induced in vitamin K absence) forms, which
have greatly reduced function.
• Warfarin interferes with the action of vitamin K epoxide reductase leading to a functional
vitamin K deficiency. (Rat poison “superwarfarin” produce similar effect)

52. VITAMIN K DEFICIENCY BLEEDING
CARBOXYLATION OF VITAMIN K DEPENDENT CLOTTING FACTORS. WARFARIN INHIBITS VITAMIN K REDUCTASE

53. VITAMIN K DEFICIENCY BLEEDING
• vitamin K deficiency occurring after the neonatal period is usually secondary to:
1. to a lack of oral intake of vitamin K,
2. alterations in the gut flora as a consequence of the long-term use of broad-spectrum
Antibiotics
3. liver disease,
4. or malabsorption of vitamin (biliary atresia, cystic fibrosis)

54. VITAMIN K DEFICIENCY BLEEDING
• Diagnosis:
i. Both PT and APTT are prolonged.
ii. There are low plasma levelsof factors II, VII, IX and X.
• Treatment
i. Prophylaxis: oral (2-5 mg/24 hr for children and 5-10 mg/24 hr for adolescents and
adults or 1-2mg I.M
ii. Active bleeding or prior to liver biopsy: slow intravenous.
iii. infusion of prothrombin complex concentrate

55. LIVER DISEASE
• Most clotting factors are produced in the liver, hence coagulation abnormalities are
expected in severe liver disease.
• Only 15% of such patients have significant clinical bleeding states, possibly because of
concomitant reduction in anticoagulation proteins.
• The most common mechanism causing the defect is decreased synthesis of coagulation
factors.
• Treatment of the coagulopathy of liver disease should usually be reserved for patients
with clinical bleeding
• Give vitamin K trial, if unresponsive, then clotting factor replacement with FFP is given.

56. Approach to a child with bleeding disorder
Bleeding
Not sick sick
Superficial bleeds Deep Bleeds
Blood culture
CBC, BT
Factor assay
Bone marrow
CBC, Bone marrow
LFT
RFT
FDP
Gene analysis
Mixing study

57. WHO BLEEDING GRADES
GRADE 0 None
Grade 1 Petechiae, ecchymoses, occult
blood loss, mild spotting
Grade 2 Gross bleeding, i.e epistaxis,
haematuria, haematemesis not
requiring transfusion
Grade 3 Haemorrhage requiring transfusion
Grade 4 Haemorrhage with haemodynamic
compromise, retinal haemorrhage
with visual impairment, CNS
haemorrhage, fatal at any location

58. CONCLUSION
The diagnosis of bleeding disorder require careful history
and physical examination supported by laboratory
investigations. Some of these disorders may be isolated or
part of other disease entity. These children should receive
evidence based care by multidisciplinary team

59. ACKNOWLEDGEMENT
Prof. B. J. Brown
Dr. Oladehin
Dr. Bayo

60. REFERENCES
1. Nelson Textbook of paediatrics, 21st edition
2. Robbins and Cotran Pathologic basis of disease, ninth edition
3. Hoffbrand’s Essential Haematology, Seventh edition.
4. Practical Guidance for Non-Specialist Physical Therapists Managing People with Hemophilia and Musculoskeletal
Complications. https://m.scirp.org/papers/98297
5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4486216/
6. https://www.stjude.org/treatment/patient-resources/caregiver-resources/patient-family-education-
sheets/hematology/platelet-storage-pool
deficiencies.html#:~:text=Delta%20storage%20pool%20deficiency%20is,constrict%20to%20help%20stop%20bleeding
7. https://www.ijmhdev.com/article.asp?issn=2635-
3695;year=2019;volume=24;issue=1;spage=18;epage=22;aulast=Okparaoka#:~:text=In%20Nigeria%2C%20there%20is
%20a,9%2C000%E2%80%9312%2C000%20PLWH%20in%20Nigeria
8. https://www.haemocare.org.ng/haemophilia/
9. https://www.nigeriamedj.com/article.asp?issn=0300-
1652;year=2019;volume=60;issue=2;spage=87;epage=91;aulast=Okoye
10. https://onlinelibrary.wiley.com/doi/full/10.1111/jth.14454#:~:text=The%20ISTH%E2%80%90BAT%20is%20an,von%20
Willebrand%20disease%20(VWD)
11. Ferri’s Fast Facts in Dermatology.
12. https://pubmed.ncbi.nlm.nih.gov/19002043/
13. https://pedsinreview.aappublications.org/content/29/4/121

61. THANK YOU