Microvascular occlusion syndromes Flashcards
What is HIT? and who gets it? what are the key risk factors?
HIT = Heparin induced thrombocytopenia
Occurs in 0.7 - 7% of patients who receive heparin (only 33 - 50% of these present with thrombosis)
Unfractionated heparin confers the highest risk
Rare in patients who receive LMWH
Does not occur with synthetic - fandaparinux
Risk Factors:
- F >M
- Major surgery
- Major trauma
- Age > 50
What causes HIT? (pathophysiology)
Platelet Factor 4 binds to epitopes on Unfractionated Heparin to form an ultralarge complex
–> exposure of an antigen on PF4 and binding of IgM
–> activation of the complement cascade
–> activation of IgG
–> platelet activation and aggregation
–> drop in platelet count and thrombosus
What does HIT show on biopsy?
Non-inflammatory
Vascular thrombosis +/ - necrosis
What is the treatment for HIT?
Stop Heparin
Anticoagulation
- needs at least 3 months if has had a thrombosis,
Agents:
- Agatroban
- Fondaparinux
NOT warfarin (increases risk of limb necrosis)
What is the normal timeframe between heparin administration and onset of HIT?
2 - 5 days
Can occur rapidly if a patient has had heparin in the last 100 days.
Can also occur after chronic exposure (eg. dialysis patients)
What are the key clinical features of HIT?
Tender
Retiform purpura
Sharply demarcated
Either at injection site or at a distant site
+ Thrombocytopenia (or 50% drop of platelets from baseline)
True or False?
Females are at higher risk of HIT than men.
True
True or False?
Patients with HIT should be anticoagulated for 3 months with warfarin
False
Contraindicated due to risk of developing gangrene.
What is the mechanism of thrombosis in a patient with Philadelphia Chromosome Negative Myeloproliferative neoplasms?
Platelet dysfunction
Number of platelets and
Platelet driven events
Note - the degree of thrombocytosis does NOT correlate with thrombotic and vascular complications
(patients with extreme thrombocytosis are at higher risk of bleeding than clotting)
What genes are associated with essential thrombocysosis, polycytheamia vera and primary myelofibrosis?
JAK2
CALR
MPL
What percentage of patients with essential thrombocysosis, polycytheamia vera and primary myelofibrosis are “triple negative” for CALR, JAK2 and MPL?
10%
What are the cutaneous manifestations of Essential Thrombocytosis?
Purpura
Haemorrhage
Livedo Reticularis
Livedo Racemosa
Erytromelalgia
Raynauds Phenomenon
Urticaria
Cutaneous small vessel vasculitis
Leg ulcers
Genagrene
Thrombophlebitis
Patients with erythromelalgia secondary to ET should be treated with what agent?
Aspirin 100mg BD
What are the expected histo findings in a patient with retiform purpura secondary to ET / PV or PMF?
Microvascular occlusion of dermal vessels or subcutaneous arterioles
What is paroxysmal Nocturnal Haemoglobinuria?
A rare hematopoietic
stem cell disorder that is associated with an increased risk of thrombosis
X Linked
What is the mechanism of thrombosis in Paroxysmal Nocturnal Haemoglobinuria?
Mutation in a gene that encodes GPI anchored protein
This protein is required for the attachment of several important membrane proteins
These proteins in turn protect the RBC from lysis
–> Red cell lysis and platelet activation
What are the cutaneous manifestations of Paroxysmal Nocturnal Haemoglobinuria?
hemorrhagic bullae,
petechiae,
leg ulcers,
non-inflammatory retiform
purpura
purpura fulminans-like presentation
A patient presents with retiform purpura.
Bloods come back with evidence of haemolytic anaemia and pancytopaenia.
What is your leading DDx?
Paroxysmal Nocturnal Haemoglobinuria
What is Thrombotic Microangiopathy (TMA)?
A syndrome characterised by microangiopathic haemolytic anaemia (RBC fragmentation and schistocyte formation) and thrombocytopaenia
TMA can primary or secondary
- Primary = TTP, Complement mediated Haemolytic Uraemic syndrome and Shiga toxin E Coli mediated HUS
What is TTP?
Thrombotic Thrombocytopaenic purpura
A subtype of Thrombotic Microangiopathy
Can be hereditary
- due to a mutation in ADAMTS1
OR most often acquired
- antibodies that reduce the function of ADAMTS to <10% of normal
ADAMTS is responsible for cleaving vWF
Presentation = fever, petichiae, thrombocytopaenia, haemolytic anaemia (RBC fragmentation), renal disease and neurological sx (confusion, headache)
What are the key features of TTP?
Fever
Thrombocytopaenia
Petichiae
Haemolytic anaeia (RBC fragments and schistiocytes)
Renal disease
Neurological Symptoms (headache, confusion)
A patient presents with fever and petichiae
Initial workup shows thombrocytopaenia, renal impairment and anaemia (with schistiocytes and RBC fragments on film)
What is your preferred Dx?
TMA,
Specifically TTP (Thrombotic Thrombocytopaenic purpura)
DDx: Complement mediated- HUS, DIC, sepsis, malignant hypertension, sclerodermoid renal crisis
What do you expect to see on biopsy of Thrombotic Thrombocytopaenic purpura (TTP)?
Simple haemorrhage
How is TMA / TTP Treated?
Plasma Exchange
Corticosteroids
A patient presents with digital retiform purpura after going skiing
What condition are you concerned about?
Disorders of cryoprecipitation / cryoagglutination
DDx:
- Cryoglobulinaemia
- Cryofibrinogeneamia
- Cryoagglutinaemia
What is sneddon syndrome?
A disease characterized by the association of
- persistent livedo reticularis or livedo racemosa
AND
- increased risk of transient
ischemic attacks (TIAs) and cerebrovascular accidents (CVAs).
What are the cutaneous features of Sneddom syndrome?
persistent and usually
widespread livedo reticularis or racemosa
Raynaud
phenomenon,
acrocyanosis,
angiomatosis,
annular atrophic lichen planus,
peripheral gangrene
