Bleeding Disorder Flashcards
Define hemostasis:
Balance between (procoagulant: blood in fluid) - (anticoagulant)
diseases associated w\ Increased procoagulant factors vs increased in anticoagulant proteins
- procoagulant: bleeding disorder
- anticoagulant: thrombotic disorder
Hemostasis is an interplay between
- vascular endothelium
- platelets
- coagulation factors
Name the 4 phases for hemostasis:
1- vascular phase
2- platelet phase
3- coagulation factors
4- fibrinolytic system
Vwf is released in which phase of hemostasis?
In the vascular phase
Describe the vascular phase of hemostasis:
- tissue injury
- Vasoconstriction
- CT exposure (sub-endothelium)
- VwF release
What is primary and secondary hemostasis & what’s the end result?
Primary: platelet phase (platelet plug)
Secondary: coagulation factors (fibrin thrombus(
Describe the platelet phase of hemostasis:
- adhesion: attach to endothelium
- activation: activated & release granules (ADP, thromboxane A2, cofactor)
- aggregation: w\VwF + w\platelets
[platelet plug]
Describe the coagulation phase of hemostasis:
- initiation: making thrombin (extrinsic)
- amplification: further thrombin (intrinsic)
- propagation: (common)
[fibrin thrombus]
What are the factors for the intrinsic & extrinsic pathway?
- intrinsic: 12, 11, 9, 8
- extrinsic: 3,7
- common: 5
What factor is responsible for stabilization of clot?
Factor 13
What is the role of protein C and protein S in hemostasis?
Inactivate factor 5 to inhibit thrombin formation
What is the role of antithrombin, heparin, A2 macroglobulin in hemostasis?
Neutralize the activity of thrombin
What is the role of TPA in hemostasis?
Converts plasminogen to plasmin to dissolve fibrin clot
Describe the extrinsic pathway
- F7 > TF > F10 > F5
Describe the intrinsic pathway
F12 > F11 > F9 > to F10 by F8
Factors to consider when evaluating a bleeding disorder:
- Gender
- Age at 1st bleed
- Site
- Frequency
- Severity
When is bleeding in a child considered normal?
If mild and over bony prominance like shaft (1-10yrs)
Usually the etiology of mucocutanous bleeding vs internal bleeding is caused by:
- mucocutanous: primary
- internal: secondary
Delayed separation of umbilical stump is associated with which coagulation factor deficiency
Factor 13 deficiency
What are the history taking clues in the neonatal state that may indicate bleeding disorder
umbilical stump, veinipuncture site, cephalohematoma, ICH
What are the history taking clues in the vaccination and surgical procedure that may indicate bleeding disorder
Circumcision, hamatoma, prolonged oozing
It’s important to inquire about family history in bleeding disorder, such as:
- bleeding in PPP in female relatives
- diagnosed bleeding disorder
What medications might be associated with bleeding in child
NSAID, warfarin, herbal (ginger, ginko, garlic)
Name the 3 bleeding disorder mimickers:
- ehlers danlos
- hemangioma
- hemorrhagic talengectasia
- child abusse
What are the symptoms of ehlers danlos syndrome
- ecchymosis
- hyperextensible joints
What are the initial testing for bleeding child
- CBC & film: HUS\TTP\leukemia
- PT: F7
- aPTT: F8, F9, F11
- both: F10, F5, F2, F1
- Fibrinogen: DIC & sepsis
In case of heparin contamination, what test is best to identify the problem?
Reptalise time
What is the mode of inheretance for hemophilia A, B, and C?
A & B: X-linked
C: autosomal recessive
In which group of population do we commonly see Hemophilia C?
Ashkenezi jews
Hemophilia A is deficient in factor
8
Hemophilia B is deficient in factor
9
When can females be affected by hemophilia A & B?
- symptomatic carrier
- lyonization
- homozygous recessive
- turner syndrome
Investigations for hemophilia:
- aPTT: prolonged
- factors: low “8 or 9 or11”
- genetic & CVS
What determines severity in hemophilia A & B patients?
Concentrations of factors
Differentiate between mild, moderate and severe hemophilia
Activity of factors, frequncy, spontanous vs major trauma, and pattern
- pattern: joint +- bleed after circumcision +- ICH [moderate]
In severe: all of them w\out +-
In mild: only till circumcision bleed
What are the complications of hemophila A or B
- arthropathy
- viral transmission
- inhibitors
What is the aim of therapy in hemophilia treatment
Improve QOL, treat on demand for mild, treat prophylactically by factors for moderate to severe.
What is the treatment for hemophilia patients
- factor replacement
- desmopressin
- antifibrinolytic
Name antifibrinolytics:
Tranxemic acid
Aminocarbonic acid
What is the desired plasma factor level of mild hemophilia A & B
20-40%
What is the desired plasma factor level of major hemophilia A & B
80-100%
What is the FDA approved monoclonal AB used to treat hemophilia
Emicizumab
What is the most common inherited bleeding disorder
VwF disease
VwF is a carrier for which factor
Factor 8
Differentiate between VwD types
- type 1: mild - quantitative
- type 2: qualitative
- type 3: severe - absent
What is the most common type in vwd?
Type 1
In vWd, which one will be affected
Aptt or pt
Aptt
In which type of vwd is riocetin reduced?
2B along with thrombocytopenia
What is the defect in type 2b vWd
Increased affinity to vWF to GP1b
In which types of vWb is desmopressin contraindicated and why?
- type 2B: thrombocytopenia
- type 3: lack of responsne
What are treatment options for vwd?
- Desmopressin
- antifibrinolytic
- factor concentration (humate-P)
- OCP
What is the role of bleeding time in platelet disorders?
Abandoned
Platelet testings include:
- count
- morphology
- flow cytometery
- PFA
- electron microscopy
What is the etiology of bernard soulier syndrome?
AR, Lack of GP1b-IX-V receptor
What are the characterstics of bernard soulier?
- prolonged PFA
- thrombocytopenia
- large platelet
What is the etiology of Glanzzman thrombasthenia
Defect in GP2b-3a
Differentiate between platelt aggregation in bernard soulier syndrome vs glanzmann thrombosthenia
Glanzzman: reacts to all except risocetin
Bernard: doesn’t react to risocetin
What is the origin of acquired bleeding disorders
Underlying disease
“Immune, liver, renal, DIC, vitamin & absorption”
What is the most common cause of acute thrombocytopenia in a healthy child?
ITP
What is the etiology of ITP?
Anti platelet glycoprotein antibodies
What are the viruses that could be associated with ITP?
EBV, CMV, H-pylori, MMR
How are the platelet distroyed in ITP?
Antibodies coat the platelet and are recognized by splenic macrophage to be destroyed
What are the findings in ITP?
All normal except for bleeding mainfestations “epistaxis, petechia, purpora, gum bleeding”
What are the positive findings of ITP?
- platelet count: <20x10^9
- platelet size: normal to large
What is the triad of ITP?
Mild bleeding - normal PE - isolated thrombocytopenia
What is the management plan for ITP?
Supportive
- w\ IVIG, Prednisolone -
What determines the prognosis of ITP?
The time from presentation
- acute: within 3 months
- presistant: 3-12 months
- chronic: >12months
What is the most common cause of pediatric thromboembolism?
Provoked (2ndary to something)
In which group of pediatric population is pediatric thromboembolism the greatest risk
Neonates
2nd peak during puberty\adolescence
How to treat pediatric thromboembolism
Acute: heparin LMW
Subacute\chronic: warfarin + Heparin LMW
What is the most common cause of acquired thrombophilia
APS antiphospholipid syndrome
What are the positive lab findings in antiphospholipid syndrome?
- positive lupus anticoagulant AB in 2 testing 2 weeks apart
- prolonged aPTT not corrected by mixing
How to treat antiphospholipid
Lifelong anticoagulant
