Pediatrics 4.8 Dr.

Rosalina Anastacio
Bleeding Disorders November 27, 2014

OUTLINE PLATELET DISORDERS

I. Bleeding Disorders Overview  About 1/3 of platelets are sequestered in the spleen
II. Platelet Disorders  2/3 circulate for 7-10 days
III. Vessel Wall Disorders
  platelets = number, size and ploidy of the megakaryocytes since this
IV. Coagulation Disorders
is a form of compensation.
REFERENCE  Platelet count influenced by:
1. Lecturer’s powerpoint o Nutritional status (malnourishment = low platelet count)
2. Recording o Menstrual cycle (“cyclic menstrual thrombocytopenia”) wherein
3. 2015B Trans women tend to easily develop bruises, with a platelet count of 120,
4. Nelson’s Textbook of Pediatrics but you do not treat this- benign.)
o Systemic condition - platelet count like in IDA, infection (Platelets
BLEEDING DISORDERS are acute phase reactants that may increase or decrease in presence
of immune-related disorders and infection)
 Bleeding disorders are a group of conditions in which there is a problem
 With Iron Deficiency Anemia (IDA) platelet can go up (recording
with the body's blood clotting process. These disorders can lead to heavy
1 hour 15min 
 somewhere there)
and prolonged bleeding after an injury. Bleeding can also begin on its
own.  In Platelet Disorders, there is increase in the number of platelets or
decrease in the function of platelets.
NORMAL HEMOSTASIS
PRIMARY HEMOSTASIS THROMBOCYTOPENIA
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 Process of platelet plug formation at sites of injury  Platelet count <150,000/mm constitutes thrombocytopenia.
 Initiated when trauma, surgery or disease disrupts vascular endothelial
PATHOPHYSIOLOGY
lining Blood exposure to the subendothelial connective tissue
1. Decreased platelet production
 Occurs within seconds of injury
 Impaired production - not enough platelets are made in the bone
 Of prime importance in stopping blood loss from capillaries, small
marrow
arterioles and venules
 Marrow infiltration with tumor or full of fibrosis
 Critical events for effective primary hemostasis
 Bone marrow failure – aplastic/hypoplastic anemias, drug effects.
1. Platelet adhesion
2. Granule release
2. Splenic Sequestration
3. Platelet aggregation
 Increased breakdown of platelets in the spleen or liver
SECONDARY HEMOSTASIS  Splenic enlargement secondary to tumor infiltration or splenic
 Consists of the reactions of the plasma coagulation system resulting to congestion due to portal hypertension.
fibrin formation – More stable and more permanent hemostatis  Enlargement of the spleen causes thrombocytopenia. 1/3 of the
 Requires several minutes for completion platelets are sequestered in the spleen and the 2/3 circulates in our
body for 7-10 days. If the platelet count is 200 right now, it means
 Particularly important in larger vessels
that you should have a platelet count of 300 if you do not have a
 Formed fibrin strands strengthen the primary hemostatic plug
spleen. If you double the size of the spleen, then 2/3 of your platelet
 Prevents bleeding from recurring hours or days after injury
will be sequestered in the spleen; the bigger the spleen the larger the
 If bleeding occurs immediately at the onset of trauma, think of a primary
sequestration of the platelets.
hemostatic problem. If there is temporary cessation of bleeding then it
occurs again hours or days after injury, consider a problem of the
3. Accelerated destruction
secondary hemostatic mechanism
 Increased destruction of circulating platelets
 Remember:
a. Non- Immune Destruction (Mechanical cause)
 Immediate – platelet problem
o Vascular prostheses, cardiac valves
 Hours/Days after injury – plasma or coagulation problem
o Disseminated intravascular coagulation (DIC)
o Sepsis
LABORATORY TESTS
o Vasculitis
PRIMARY HEMOSTATIC SYSTEM
1. Platelet count – platelet count should be at least 150,000
2. Bleeding time Abnormal vessels
If the platelet count is normal and the function is defective, then you Fibrin Thrombi
would expect an increase in the bleeding time, and problem in your Intravascular Thrombocytopenia
primary hemostasis.

PLATELET COUNT VS PROPENSITY TO BLEED

 Platelet count >100,000/ul Normal BT Shorten Platelet Survival
 Platelet count 50,000-100,000 Mildly prolonged BT
 Platelet count <50,000 bleeding after minor trauma
 Platelet count <20,000  spontaneous bleeding (reason for blood
transfusion in dengue hemorrhagic fever) Non-Immunologic
Thrombocytopenia
e.g. TTP, HUS, DIC, Vasculitis

Figure1. Non-immunologic Thrombocytopenia

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b. Immune Destruction (Involvement of immune complements) COURSE OF ILLNESS

o Autoantibodies to platelet antigen  60% recover in 4-6 weeks
o Drug associated antibodies  >90% recover in 3-6 months
o Circulating immune complexes (SLE, Viral, Bacterial infections)  The remaining who do not recover after 6 months are those who will
o To have a diagnosis of SLE, there should be thrombocytopenia. take a form of CHRONIC ITP (4-5%).

Accelerated Platelet Destruction Coated with:

CHRONIC ITP
 Indolent form of thrombocytopenia
Platelet
 Platelet count usually is much higher than in the acute form. A patient
Antibody
with sudden onset of a platelet count of 10 is most likely just an acute ITP
Immune complexes
case. But an older patient, usually female, with a platelet count as high as
Complement 60-80, will most likely goes into the chronic form of ITP.
 Condition persists for years
 Most common in FEMALES 20-40 years old (F:M ratio 3:1)
Increase Mononuclear Phagocytic Clearance  Autoimmune Disorder with antibodies vs. target antigens
- occurs in the spleen
DIAGNOSIS
 Bone marrow examination
 ANA – to rule out other conditions such as Hepatitis, CMV, SLE
Immnuologic Thrombocytopenia
e.g. ITP, Drug-induced TREATMENT
1. Glucocorticoids
Figure 2. Immunologic Thrombocytopenia 2. Antibody preparations for phagocytic blockage to “block” the immune
reaction decrease the antibody production.
DIAGNOSIS o Intravenous Immunoglobulin (IVIG)
 CBC and Platelet count o Anti-RhD (Win Rho)
 Peripheral Blood film examination o Very good treatment reserved for patient with very low platelet
 Bone marrow morphology (BMA/Biopsy) count and bleeding that is potentially fatal (e.g. Presence of GI
o Increased megakaryocytes bleed, severe headache)
o Confirm diagnosis by doing posterior iliac crest aspiration 3. Emergency Splenectomy- in very severe bleeding even with massive
 Splenic size platelet transfusion because it is here that platelets are sequestered.
o CBC normal but with enlarged spleen could be splenic sequestration Platelet transfusion is not a treatment, as the platelets will only be
destroyed by antibodies are when given. Platelet concentrates may help in
IMMUNOLOGIC THROMBOCYTOPENIA/ time of massive bleeding.
IMMUNE THROMBOCYTOPENIC PURPURA (ITP) 4. Immunosuppressive drugs
 Mostly seen on pediatric patients o Azathioprine
 Adult equivalent: Thrombotic thrombocytopenic purpura o Cyclophosphamide
 Types: Acute ITP and Chronic ITP o Vincristine

ACUTE ITP FUNCTIONAL PLATELET DISORDERS

 Sudden onset of severe thrombocytopenia  With a normal platelet count and is bleeding, think of a functional
 Preceded by URTI or Viral exanthema in early stages platelet disorder; also known as THROMBOCYTOPATHY.
 Common in children: 90% of pediatric ITP
 Rare in adults: <10% of post pubertal patients with ITP VON WILLEBRAND DISEASE
 Most common inherited bleeding disorder (1:800 to 1,000)
CLINICAL MANIFESTATIONS  Inherited as autosomal dominant trait
 Skin and mucous membrane bleeding, not in the deep tissues  Due to reduction in von Willebrand Factor (vWF) (N=10 mg/L)
 NORMAL PHYSICAL EXAM, but with bleeding  Von Willebrand Disease is not usually diagnosed because confirmatory
 Remember: The platelet so the only one affected here, so there is only test for this is not yet available in the country. The pattern of bleeding is
skin and mucosal hemorrhage present. on the skin and mucosa, which is contrary to the pattern of bleeding on
clotting problems which is usually seen as larger and deeper tissues like
 This is usually a patient who is running and playing around, except for
muscle and fascia.
petechial and other bleeding manifestation
CLINICAL MANIFESTATIONS
DIAGNOSIS
 Mild cases - bleeding after surgery or trauma
 CBC:
o NORMAL RBC, WBC  Severe cases - spontaneous mucosal bleeding
o THROMBOCYTOPENIA  Patients with VWD usually have symptoms of mucocutaneous
 Bone Marrow Aspiration (BMA) - confirmatory hemorrhage, including excessive bruising, epistaxis, menorrhagia, and
o megakaryocytes – compensatory mechanism of the BM postoperative hemorrhage, particularly after mucosal surgery, such as
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o To confirm do posterior iliac crest aspiration tonsillectomy or wisdom tooth extraction.
 Because a teenager's menstrual history is usually put in the context
of other family members, excessive menstrual bleeding is not always
recognized as being abnormal, because others in the family may be
affected with the same disorder.
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 If a menstruating female has iron deficiency, a detailed history of CLINICAL MANIFESTATIONS

bruising and other bleeding symptoms should be elicited and  Purpuric or urticarial rashes on extensor surfaces of arms and legs and
further hemostatic evaluation undertaken. on buttocks (palpable rashes). Mostly symmetrical. If you see
 Because VWF is an acute-phase protein, stress will increase its level. asymmetrical purpuric rashes and beyond the buttocks, HSP is ruled out.
Thus, patients may not bleed with procedures that incur major stress,  Polyarthralgia because of the inflammation of small capillaries and
such as appendectomy and childbirth, but may bleed excessively at arterioles
the time of cosmetic or mucosal surgery.  Arthritis
 Colicky abdominal pain
LABORATORY FINDINGS  Hematuria (focal glomerulonephritis)
 Normal Platelet, Prolonged bleeding time  TRIAD: SYMMETRICAL PURPURA, POLYARTHALGIA AND ABDOMINAL
 ↓ plasma vWF concentration PAIN (Remember!)
 Ristocetin cofactor assay
 ↓ Factor VIII activity – so it can manifest as prolonged PTT LABORATORY FINDINGS
 Normal coagulation tests
TREATMENT  Done to rule out other conditions since all parameters are expected to be
1. Factor VIII concentrate, not platelet concentrate normal.
2. Desmopressin (DDAVP) – very good preparation esp. for mucosal and
gum bleeding. Not available in the Philippines. TREATMENT
 Glucocorticoids provide symptomatic relief of colicky abdominal pain,
VESSEL WALL DISORDERS polyarthralgia, but have no effect on the course of illness.
 “NON THROMBOCYTOPENIC PURPURA”
 Bleeding usually mild, confined to the skin and mucous membranes PROGNOSIS
 Classical tests of hemostasis (PT, PTT, BT) normal  Good
 Remember: All bleeding parameters here are expected to be normal.  5-10% will develop chronic nephritis
The bleeding here is not due to platelet or coagulation problems.  Small percentage: fatal due to acute renal failure
 Presents as a vascular purpura secondary to:
o Damage to capillary endothelium METABOLIC AND INFLAMMATORY DISORDERS THAT GIVE RISE TO
o Abnormalities in the vascular sub endothelial matrix VASCULAR PURPURA
[NOT DISCUSSED]
 Due to endothelial damage:
HEMOLYTIC UREMIC SYNDROME o Infections: Rickettsiae  endothelial damage
 Disease of infancy and childhood o Drugs
 Closely resembles TTP  Sulfonamide
 Often preceded by minor febrile/ viral illness  Penicillin
o Usually follows an episode of acute gastroenteritis, often triggered  Allopurinol
by Escherichia coli 0157:H7. Shortly thereafter, signs and symptoms  Scurvy (Vitamin C deficiency)  perifollicular skin bleeding, GI, GUT,
of hemolytic anemia, thrombocytopenia, and acute renal failure bleeding  hydroxyproline synthesis collagen synthesis 
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ensue bleeding.
 Proposed Mechanism: infection or immune complex- mediated  Scurvy, chronic corticosteroid therapy, and severe malnutrition are
 No evidence of DIC associated with “weakening” of the collagen matrix that supports the
 Problem is localized in the kidney - Hyaline thrombi in afferent arterioles blood vessels. Therefore, these factors are associated with easy bruising,
and glomerular capillaries are involved and particularly in the case of scurvy, bleeding gums and loosening of the
 Characterized by morphologically abnormal RBCs, with the presence of teeth. Lesions of the skin that initially appear to be petechiae and purpura
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helmet cells, spherocytes, schistocytes, burr cells, and other distorted may be seen in vasculitic syndromes, such as SLE.
forms.
 Thrombocytopenia despite normal numbers of megakaryocytes in the LABORATORY FINDINGS
marrow indicates excessive platelet destruction.  Secondary Hemostatic System
 Evaluation of the urine shows protein, RBCs, and casts.  PTT- Tests Intrinsic Limb
 XII, HMWK, PK, XI, IX, VIII
TREATMENT  PT – test extrinsic or tissue factor (dependent pathway)
 No effective treatment
 Dialysis  5% decrease in Mortality Rate (initial) COAGULATION DISORDERS
 10-50% residual chronic renal impairment FACTOR VIII DEFICIENCY - HEMOPHILIA A
 Most common inherited coagulation disorder
HENOCH-SCHONLEIN PURPURA (HSP)  AHF (Factor VIII)- activates Factor X (which will eventually give rise to
 Palpable purpura, raised mostly on both extremities. fibrin formation)
 Anaphylactoid purpura  Incidence: 1:10,000
 Distinct, self-limited type of vasculitis, in children and young adults
 Acute inflammatory reaction in the capillaries and mesangial arterioles CLINICAL MANIFESTATIONS
will cause an increase vascular permeability causing exudation and  Bleeding into soft tissues, muscles and weight-bearing joints
hemorrhage into the skin and other body organs (liver, kidneys, CNS) o <1% FVIIIsevere disease
 Condition preceded by URI or streptococcal pharyngitis or associated o >5% FVIIIsymptomatic only
with food, drug allergies, or immunizations o >8% FVIIIasymptomatic
 Most common cause of vascular purpura  Bleeding occurs hours or days after injury

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 Although bleeding may occur in any area of the body, the hallmark of DISSEMINATED INTRAVASCULAR COAGULATION
hemophilia is hemarthrosis. Bleeding into the joints may be induced by  Clotting factors will be consumed and your platelets will also be consumed
minor trauma; many hemarthroses are spontaneous. such that there will be Explosive and life- threatening conditions. In some
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 The earliest joint hemorrhages appear most commonly in the ankle. In the rare cases, it is mild and subclinical.
older child and adolescent, hemarthroses of the knees and elbows are
also common; they complain of a warm, tingling sensation in the joint as ETIOLOGY
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the first sign of an early joint hemorrhage.  Obstetrical catastrophies (like placenta previa with massive bleeding )
 Metastatic malignancy
DIAGNOSIS  Massive trauma
 Prolonged PTT  Bacterial sepsis
 Decreased Factor VIII Asssay  Massive burns
 Normal PT, Platelet count, Bleeding Time
CLINICAL MANIFESTATION
TREATMENT  Bleeding anywhere
Early treatment is more effective, less costly, and lifesaving.  Skin and mucous membrane
1. Anti-inflammatory Drugs  Surgical incision
 DO NOT GIVE ASPIRIN – anti-platelet will add insult  Venipuncture sites
 Give CoX-2 inhibitors  Catheter sites
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2. Replacement Therapy  Peripheral Acrocyanosis – due to blood supply
 Factor VIII concentrates 1u increase up to 2%/KBW  Thrombosis
o Treatment of choice because of less volume, less protein that
may cause sensitization, less transmission of diseases such as DIAGNOSIS
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hepatitis and CMV. The only problem here is the cost.  Consumption of clotting factors and platelets leading to :
 Cryoprecipitate – cheaper and contains Factor VIII and Fibrin  platelet count
 Fresh Frozen Plasma – contains all clotting factors  ↑PT, PTT, TT (Thrombin time)
o Disadvantage: more volume is needed, has increased risk of  (+) Schistocytes or fragmented red cells
hypersensitivity since it contains more proteins.  Increased fibrin degradation product (FDP)
 Desmopressin (DDAVP) – especially in mucous membrane
hemorrhages. TREATMENT
 Prophylaxisis for surgery and dental procedures  Treatment of underlying cause
o Factor VIII PLUS E-aminocaproic Acid OR  If with severe blood loss, replace the blood loss. If with severe
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o Tranexamic Acid infection, give aggressive antimicrobial .
 Control bleeding or thrombosis
COMPLICATIONS OF TREATMENT 1. Fresh Frozen Plasma (FFP)
 Hepatitis, HIV – due to blood transfusion 2. Platelet concentrates
 Fe-deficiency anemia – due to repeated bleeding 3. IV Heparin
 Coomb’s (+) Hemolytic Anemia  Prophylaxis for chronic DIC: periodic IV Heparin
 Development of Factor VIII inhibitors-most dreaded complication. In spite
of transfusion of FVIII, bleeding does not stop.
CASE
FACTOR IX DEFICIENCY- HEMOPHILIA B Gerard, 5y/o, male, who is admitted because of sudden onset of
 Incidence: 1:100,000 ecchymoses all over the body 3 days PTA.
 Clincal Manifestations: Same as Hemophilia A
 Diagnosis:  Factor IX assay HPI:
 Treatment: Fresh Frozen Plasma (FFP), Factor IX Concentrates  3 weeks PTA, he had mild cough and colds which spontaneouly resolved
We do not give cryoprecipitates because it contains only Factor VIII and after 5 days.
fibrin.
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 5 days PTA, there were few pinpoint reddish spots (petechiae) on the
abdomen. However, there were no other associated signs and symptoms.
ACQUIRED COAGULATION DISORDERS  3 days PTA, ecchymosis developed all over the body. No other associated
VITAMIN K DEFICIENCY signs and symptoms.
 Most common cause of acquired coagulation disorder
 3 Major Causes: PHYSICAL EXAMINATION:
o Inadequate dietary intake  Walking, running around, active, not in any form of distress.
o Intestinal malabsorption  (+) ecchymosis all over the body
o Loss of storage sites (Hepatocellular Disease)  (-) overt bleeding: gum bleeding, hematochezia)
 Diagnostic: ↑PTT (Prothrombin Time)  Others unremarkable.
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 Deficiency of Factors II, VII, IX, X, protein C and protein S
o Mild deficiency - Factor VII,  protein C (prolonged PT) LABORATORY:
o Severe, prolonged deficiency, liver is damaged- prolonged PT, PTT Hct 12.5g/L N
 Treatment: Vitamin K, Fresh Frozen Plasma (FFP) for severe hemorrhage Hct 37 N
Hgb 11.5 N
Neutrophils 52% N
Lymphocytes 46% N

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Eosinophils 4% N
Platelet Count 30,000 Decreased
Bleeding Time 3 min N
Protime 12.4 sec N
PTT 29.0 sec N

DIAGNOSIS: ACUTE ITP

Ruled out:
 Acute Leukemia - since N WBC, normal PE
- in leukemia, (+) hepatomegaly, splenomegaly, lymphadenopathies
pallor, proliferation of abnormal cells (↑WBC, abnormal
differential count since blast cells will predominate.
 Hemophilia – since Platelet, N PTT
- in hemophelia, N platelet count, N Protime, Prolonged PTT
 Von Willebrand Disease – ruled out since N bleeding time, Platelet
- not consistent with the patient’s history, no family history
- N platelet time, prolonged bleeding time, prolonged PTT

REMEMBER!!!
 Von Willebrand Disease - most common inherited BLEEDING disorder.
 Hemophilia - most common inherited COAGULATION disorder.

Edited by: Lilai Omengan 

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