Transcript Bleeding Disorders Approach a Child with Purpura

 A 4-year-old female.
 Referred to the hematology department.
SCENARIO
 C/C:
 easy bruising and "rash" for 3 days.
 HPI:
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She developed an acute onset of easy bruising
and "rash" 3 days ago.
She has not had epistaxis, oral bleeding, gross
blood in urine or stools.
No hemarthrosis.
No joint pain.
 HPI:
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SCENARIO
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No fever.
No appetite change,
No weight loss.
She had URTI symptoms approximately 2
weeks ago.
 Travel Hx.:
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No travel history..
 Family Hx.:
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She has 2 older brothers, neither of whom
have had bleeding symptoms.
Family hx. is –ve for any bleeding tendency.
No hx. of malignancy or autoimmune diseases.
 Past Hx.:
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SCENARIO
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No past hx of a similar problem.
No past hx. of prolonged bleeding of wound or
dental extraction.
She had an URTI 2 weeks ago.
 Physical Examinations:
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Vital signs:
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Normal.
Growth parameters:

Normal.
 Physical Examinations:
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Head and Neck:
 No bleeding or bruises.
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Chest Examinations:
SCENARIO
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Heart & Lung are normal.
Abdominal Examinations:
No tenderness.
 No organomegally.
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She has diffuse petechial rash is noted on
her neck, trunk, extremities and groin. It is
non-blanchable or varying ages.
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CNS Examination:
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Normal.
 Lab.:
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SCENARIO
CBC:
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Hb: 12.8 g/dl.
Hct: 38.5 %.
WBC: 6,000 with normal differential.
Platelets: 5,000 “low”
 PT: 12 seconds.
 PTT:32 seconds.
 Peripheral blood smear:
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Normal RBCs & WBCs.
Platelets: reduced in number and large size.
 Dx.:
SCENARIO
ITP
► Bleeding Disorders
Review Hemostasis
Hemostasis
 It is the process to stop blood loss.
 Three Phases:
Primary Hemostasis
PRIMARY HEMOSTASIS
 PRIMARY HEMOSTASIS:
Endothelium Injury
Release of
vasoconstrictors
Exposure of Subendothelial
Collagen
Platelets Adhesion:
vWF adhers Platelets to
Subendothelial Collagen Via
GPIb
Platelets Aggrigation
These Factors (ADP & TXA2)
Stimulate Platelets to bind
together via GPIIb & GPIIIa
Platelets
activated and
release ADP &
TXA2
PRIMARY HEMOSTASIS
 PRIMARY HEMOSTASIS:
Primary Hemostasis
Platelet
GPIIb/GPIIIa
vWF
•Ends with
formation of
platelets plug.
GPIIb/GPIIIa
Platelet
GPIb
vWF
•Assessment:
•Platelets Counts:
•150 – 450 X 103/ml.
•Bleeding Time BT:
•<8 mins.
Secondary Hemostasis
SECONDARY HEMOSTASIS
 SECONDARY HEMOSTASIS:
Intrinsic
Extrinsic
PT/
INR
aPTT
Thrombin
PT
aPTT
TT
 Depends on the activities of coagulation factors.
 Ends with formation of Fibrin clot.
Secondary Hemostasis
PT: Prothrombin Time:
- Normal: 11 – 24 sec.
aPTT: activated Partial Thromboplastin
Time:
- Normal: 22 – 35 sec.
INR: International Normalization
Ratio:
- Normal: 0.9 – 1.2
Secondary Hemostasis
PT: Play Tennis:
- Tennis is played outside → Extrinsic Pathway.
PTT: Play Table Tennis:
- Table Tennis is played inside → Intrinsic Pathway.
Resolution
Secondary Hemostasis
Resolution:
Disorders of Primary
Hemostasis
Primary Hemostasis
Platelet
GPIIb/GPIIIa
vWF
GPIIb/GPIIIa
Platelet
GPIb
vWF
•Characterized by superficial bleeding. petechiae, ecchymoses
Primary Hemostasis
Disorders of
Disorders of Primary Hemostasis
Platelets
Disorders
Low Platelets
Count
Platelets
Dysfunction
“Thrombophillia”
“Thrombocytopenia”
↓Production
Aplastic
anemia
↑Destruction
ITP
TTP
HUS
Sequestration
Splenomegaly
Heridatery
•Bernard Soulier Syndrome:
“GPIb Deficiency”
•Glanzmans Syndrome:
“GPIIb/IIIa Deficiency.
Acquired
•Drugs.
•Uremia.
Immune Thrombocytopenic
Purpura ITP
ITP:
•Common cause of thrombocytopenia.
•Peak age: 2 – 6 years.
•M=F.
ITP
•Pathophysiology:
•Antibodies bind to platelets
membranes → destruction by spleen.
C/P:
•50% presents 1-3 weeks after viral illnesses
ITP
(URTIs).
•Sudden onset of petechiae, purpura,
echymosis, epistaxis,...
•No hepatomegaly or splenomegaly.
Lab. Findings:
•CBC:
•Platelets count:
•Mild: < 100,000/mm3.
ITP
•Moderate: < 50,000/mm3.
•Severe: < 20,000/mm3.
•Bleeding Time BT: prolonged.
•PT & aPTT are normal.
Treatment:
•Mild cases:
•No treatment is required.
•Severe cases: (Platelets count < 50,000/mm3 ):
ITP
•Prednisolon.
•IVIG.
•Dangerous bleeding (e.g., intracrainial):
•Platelets.
•High dose steroids.
•IVIG.
•Emergency splenectomy.
Treatment:
•Chronic ITP:
•Cytotoxic drugs: e.g., cyclophosphamide.
ITP
•Splenectomy if not responding to
medical treatment.
Henoch-Schönlein
purpura (HSP)
Henoch-Schönlein
purpura (HSP)
Henoch-Schönlein purpura (HSP):
•Also called:
•Allergic Purpura, or
•Anaphylactoid Purpura.
HSP:
•Etiology:
•Unknown.
ITP
•Considered as hypersensitivity small
vessels vasculitis.
•In most of cases, there is a history of
preceding URTI.
•Age: 2 – 10 years.
•M>F.
HSP:
• C/P:
ITP
•Skin rash:
•Purpuric rash.
•Distributed mainly on
the lower limb and
buttock.
HSP:
• C/P:
•Joints: Arthritis.
ITP
•Abdomin:
•Abdominal pain.
•Bleeding: hematemesis or melena.
•Intussusception.
•Renal:
•Edema, HTN, hemturea, oligurea.
•Normal serum complements.
HSP:
• C/P:
•CNS:
ITP
•RARE.
•Convulsion.
•Stroke.
•Facial palsy,..
HSP:
ITP
• Lab Findings:
•Platelets count: normal.
•BT, PT & aPTT: Normal.
•Serum complements: Normal.
•↑ serum IgA.
•Ocuult blood in stool.
•US abdomen: intusseception.
•Urine analysis & RFTs.
HSP:
•Renal functions should be followed up to 1
ITP
year after recovery.
•Treatment:
•Analgesic:
•to control abdominal pain and
arthritis.
•Prednisolon:
HSP:
•Prognosis:
•Complete recovery is the rule unless
ITP
severe renal disease occurs.
Von Willebrand’s Disease
vWD:
•Quantitative or qualitative defect in vWF.
vWD
•vWF has two major functions:
•Needed for platelets adhesion.
•Carries factor VIII.
•Therefore, vWD affects both
primary & secondary hemostasis.
vWD:
•Classification:
vWD
• Mild quantitative
defect.
• The most common.
Type I
Autosomal
Dominant.
• qualitative defect.
• vWF dysfunction
TypeII
Autosomal
Dominant.
• severe total
quantitative defect.
• No vWF produced.
Type III
Autosomal
Recessive.
vWD:
•C/P:
•Mucosal and cutaneous bleeding.
vWD
• Easy bruising.
•Epistaxis.
•Menorrhagia.
•In severe cases:
•Soft tissue hematomas,
•GI bleeding.
•Hemarthroses.
vWD:
•Investigations:
vWD
•Platelets count: normal.
•BT: increased.
•PTT: prolonged.
•VIII: decreased.
vWD:
•Treatment:
vWD
•Desmopressin (DDVP).
•Factor VIII concentrate.
Disorders of Secondary
Hemostasis
Disorders of Secondary Hemostasis
Disorders of
Secondary Hemostasis
Congenital
•Hemophilia
Acquired
•Liver diseases.
•Vitamin K deficiency.
•DIC.
•Present with deep bleeding: Joint, muscles, GI tract, GU tract,
•Excessive prolonged post-traumatic bleeding.
Hemophilia
Hemophilia:
Hemophilia
•X-linked Recessive.
Hemophilia:
Hemophilia
C/P:
•Deep bleeding: 5Hs:
•Hemarthrosis.
•Hematoma.
•Hematochezia.
•Hematuria.
•Head hemorrhage.
•Easily bruising.
•Prolonged wound bleeding…
Hemophilia
Hemophilia:
Types:
• Factor VIII
deficiency.
• Factor IX
deficiency.
• Factor XI
deficiency.
• “Christmas
disease”
Hemophilia
A
Hemophilia
B
X-Linked Recessive
Hemophilia
C
Autosomal
Recessive
Hemophilia
Hemophilia:
Investigations:
•aPTT: prolonged.
•PT (& INR): Normal.
•Factor assay.
Hemophilia
Hemophilia:
Treatment:
•Hemophilia A:
•Desmopressin (DDVP).
•Recombinant Factor VIII.
•Anti-fibrinolytic agents (e.g.
tranexamic add)
•Fresh frozen plasma???
Hemophilia
Hemophilia:
Treatment:
•Hemophilia B:
•Recombinant Factor IX.
•Anti-fibrinolytic agents (e.g.
tranexamic add)
•Fresh frozen plasma.
Hemophilia
Hemophilia:
Treatment:
•Hemophilia C:
•Recombinant Factor XI.
•Anti-fibrinolytic agents (e.g.
tranexamic add)
•Fresh frozen plasma.
Approach a Patient with
Purpura
Definition of Purpura:
Purpura
•Red, nonblanching maculopapular lesions.
•Caused by intradermal capillary bleeding.
Causes:
Purpura
•Caused by disorders affecting platelets or
blood vessels.
History:
•Age ?
History
•Onset? Acute vs. Chronic.
•Bleeding in other site:
•Mucus membranes.
•Joints.
•Orifices.
•Easily bruising.
•Prolonged wound bleeding.
•Associated symptoms:
•Abdominal pain.
•Bloody stool.
•Hematemesis.
•Hematurea.
•Joints pain.
History
History:
•Associated symptoms:
•Fever.
•Bone pain.
•Polyurea? Oligurea?
•Lethargy?
•Headache?
•Symptoms of anemia?
•Appetite?
•Weight loss?
•Hx. of recent URTI “during last 3 – 4 weeks”.
•Drug use
•Family history
•Maternal history
•Social history
Physical Examinations
Physical Examinations:
•Genaeral Look.
•Vital signs.
•Growth parameter.
Physical Examinations
Physical Examinations:
•Characteristic of rach:
•Distribution.
•Color.
•Size.
•Palpable?
•Blachable/Non Blanchable.
•Bleeding in mucus membrane e.g., gum,..
•Nose? Epistaxis.
•Pallor?
Physical Examinations
Physical Examinations:
•Retinal hemorrhage?
•Joint examination.
•Lymph nodes?
•Abdominal examination:
•Tenderness?
•Organomegally?
•Rectal examination.
Lab.:
Investigations
•CBC.
•Coagulation profile.
•PT, INR.
•aPTT.
•TT.
•Factor assay?
•Biopsy of rash:
•IgA deposits “ Leukocytoclastic vasculitis” -- HSP.
•BM:
•If suspect leukemia; orgaanomegally,bone
pain, lymphadenopathy, prolonged
fever,…