HIT: risk factors (3)
- Unfractionated heparin > LMWH - Therapeutic dose > Prophylactic dose - Bovine > Porcine
Which anti-thrombotic agents can be substituted for heparin after a diagnosis of HIT (3)?
Lepirudin Argatroban Fondaparinux
What are the 2 diagnostic tests available for HIT?
- ELISA - Platelets 14C serotonin release assay
5 drugs leading to thrombopenia
- Sulfas - Penicillin - Quinines - Procainamide - Levodopa - Gold salts - Interferon alfa
What is Upshaw-Schulman syndrome?
Congenital TTP, caused by mutation (AR) in ADAMTS13
How is confirmed the diagnosis of TTP?
- Confirmation of decreased ADAMTS13 activity - Screening for anti-ADAMTS13 auto-Ab
TTP: - How many are secondary? - Name 3 causes of secondary TTP
- 15% - Pregnancy, drugs, infections (viral or bacterial), collagen vascular disorders, malignancy, pancreatitis
TTP treatment a) Congenital b) Acquired
a) Prophylactic FFP infusions b) Plasma exchange; Glucocorticoids often given as adjunct, although advantage not proven Rituximab for refractory cases
Which lesions are associated with Kasabach-Merritt phenomenom?
Tufted angioma Kaposiform hemangioendothelioma
- Diagnosis? - Non MSK complications
Osteopetrosis Syndrome associated with osteoclasts dysfunction, leading to impaired bone modelling and repair Leads to skeletal fragility despite increased bone mass and hematopoietic insufficiency, delayed tooth eruption, nerve entrapment syndrome, short stature
Osteopetrosis: treatment options
Only curative option: HSCT, to be done ASAP re: neurological impairment early in course of disease and often irreversible
Calcitriol, IFN-gamma and prednisone can slow down progression
- Risk for future pregnancies
- how should future pregnancies be managed?
- Usually severity of NAIT increases with each pregnancy
- Percutaneous umbilical cor sampling @ 20-22 weeks for fetal platelet count and platelet antigen typing
Maternal IVIG weekly
NAIT: what proportion of patients develop ICH?
What other Sx are seen?
15% (including 50% in utero)
Petechias, hematomas, GI bleeding
NAIT: what is the duration of the thrombopenia?
Name 3 sides effects of TPO agonists, using in the treatment of ITP
Both: myelofibrosis and thrombo-embolic events (adult studies, seems well tolerated in children)
Name 5 situations where ALPS should be investigated?
- Unexplained auto-immune disease
- Auto-immune disease affecting at least 2 organs
- Unexplained lymphoproliferation
- Cytopenias of at least 2 lineages
- Single cytopenia withhypergammaglobulinemia
What are the 2 required features required for a diagnosis of ALPS?
1. Lymphadenopathy and/or splenomegaly of non-infectious origin
for at least 6 months
2. Elevated double-negative alpha/beta T-cells
(i.e. > 1.5% of T-lymphocytes or >2.5% of all lymphocytes)
What genetic mutations are associated with ALPS?
FAS, FASL, CASP10
How is the diagnosis of BSS confirmed?
- Platelet aggregation test: failure to agglutinate in presence of ristocetine; otherwise normal aggregation with other agonists
- Flow cytometry: decreased expression of GP1B/IX complex
- Molecular studies: mutation of GP1BA, GP1BB, GP9
What is contained in:
- Alpha granules?
- Delta granules?
- Alpha: "the big stuff" such as prothrombotic and proangiogenic factors and antithrombotic and antiangiogenic factors e.g. VWF, thrombospondin, PF4
- Delta: small molecules e.g. calcium, serotonin, ADP, ATP, etc.
- Associated mutations?
- Populations at risk
- HPS1 to 9 (autosomal recessive)
- High frequencies in certain populations, e.g. Puerto Rico
Clinical features associated with Hermansky-Pudlak syndrome (6)
- Oculo-cutaneous albinism
- Visual features: decreased visual acuity, photophobia, rotatory nystagmus
- Mild to moderate bleeding diathesis, following a storage pool disorder
- Granulomatous colitis
- Pulmonary fibrosis (HPS 1 & 4)
- Neutropenia (HPS 2)
Dense granules defects:
- Name 3 examples
- Hermansky-Pudlak syndrome
Describe diagnostic tests specific for dense granules defects
- Whole-mount microscopy
- Serotonin release assays or ATP/ADP release assays
Which clinical features are associated with Griscelli syndrome?
- Silver hair
- Partial albinism
- Mild bleeding diathesis (plt function disorder)
- Neurologic defects
Bonus! Associated mutation: RAB27A
List 2 disorders marked by alpha-granules defect?
- Gray platelet syndrome (NBEAL mutations)
- ARC: arthrogryposis, renal dysfunction, cholestasis syndrome (VPS33B or VPS16B mutation)
Name mutations associated with essential thrombocytosis (3)
- JAK 2
What treatment modalities are available for essential thrombocytosis?
- Low dose aspirin
- Cytoreductive therapies: hydroxyurea, interferon-alpha
Work up thrombocytosis
- Peripheral smear
- Iron work up
- BCR-ABL1 rearrangement
- Mutation status for JAK2, CALR, MPL
- Bone marrow aspirate and biopsy
3 complications associated with ET