144 - Cryoglobulinemia and Cryofibrogenemia Flashcards
Circulating immunoglobulins in both serum and plasma that reversibly precipitate or gel upon cold exposure
Cryoglobulins
Result form precipitation of fibrinogens on cold exposure and are detectable only in plasma samples, not serum
Cryofibrinogens
Cryoglobulinemia and cryofibrogenemia: conditions that lead to microvascular occlusion
Type I cryoglobulinemia
Cryofibrinogenemia
Cryoglobulinemia and cryofibrogenemia: conditions that lead to small- and medium-sized vessel vasculitis
Types II and III cryoglobulinemia
Consist of a single monoclonal immunoglobulin, typically IgM
Type I cryoglobulins
Represent a mixture of 2 Ig components: polyclonal immunoglobulins associated with a monoclonal Ig that exhibits rheumatoid factor activity
Type II cryoglobulins
Classic underlying disease in Type II cryoglobulinemia
HCV infection
Mixture of polyclonal immunoglobulins or polyclonal Ig-nonimmunoglobulin cryoprecipitates
Type III cryoglobulins
Polyclonal IgG associated with a mixture of polyclonal and monoclonal (oligoclonal) IgM
Type II-III cryoglobulins
Mixed cryoglobulinemia without an identifiable cause
Essential mixed cryoglobulinemia
Essential mixed cryoglobulinemia is more common in _____ with an average onset of _____
Females
54 years
The vast majority (>90%) of mixed cryoglobulinemias occurs in association with
Chronic HCV infection
Most frequent manifestation of cryoglobulinemia
Cutaneous lesions
Infarction, hemorrhagic crust, ulcers, and lesions on the head and oral or nasal mucosa are relatively more common in
Type I cryoglobulinemia
Than in mixed cryoglobulinemia
Most common presentation of Type II and III cryoglobulinemic vasculitis
Intermittent orthostatic palpable purpura, frequently observed in the afternoon when highest cryoglobulin concentrations are present
Histopathologic hallmark of mixed cryoglobulinemia
Leukocytoclastic vasculitis
Most common extracutaneous manifestations in patients with mixed cryoglobulinemic vasculitis
Weakness
Arthralgias or arthritis
Metlzer triad
Purpura
Arthralgias
Weakness
Most frequently encountered hematologic malignancy in Type I cryoglobulinemia
Non-Hodgkin B-cell lymphoma
Type I cryoglobulins tend to precipitate within the first ______, where Type III cryoglobulins may require
24 hours
7 days
A cryocit of at least _____% is considered positive
2
Reference serum viscosity is between 1.4 and 1.8, whereas most symptomatic patients have values between
5 and 8
Typical pattern of hypocomplementemia in mixed cryoglobulinemia
Low or undetectable C4
Normal or relatively normal C3 levels
Patients with non-HCV mixed cryoglobulinemia have overall (lower/higher) mortality rate than their HCV-positive counterparts
Higher
Most common cause of death in HCV patients with mixed cryoglobulinemia, followed by complications related to liver and cardiac involvement
Infection
Organs most vulnerable to acute severe complications directly caused by cryoglobulins
Nervous system
Kidneys
Treatment of choice for type I cryoglobulinemia
Etiologic treatment
Patients with mild to moderate HCV-associated cryoglobulinemic vasculitis without major organ failure are best treatment with
PEGylated interferon alpha-2b
Ribavirin
Current gold standard
Applicability of _____ in renal insufficiency is reduced because of drug accumulation
Ribavirin
Side of effect of ribavirin requirng pausing or dosing adjustments
Hemolytic anemia
Preferred therapeutic regimen in patients withHCV-associated severe or refractory/relapsing disease, renal involvement, and in those whom rapid clinical response is needed
Rituximab combined with Peg-IFN-alpha/ribavirin
Should not be used in patients with overt skin ulceration because of interference with wound healing
Rituximab
A recent report has pointed to a severe complication with worsening of cryoglobulinemic vasculitis syndrome in patients with high baseline levels of mixed cryoglobulins receiving
Rituximab
_____% of healthy persons may have demonstrable amounts of cryofibrinogen
2-9
Patients with cryofibrinogenemia are usually diagnosed between the _____ decades of life, with a _____ predilection
Fifth and seventh
Female
Most frequent clinical presentation of cryofibrinogenemia
Palpable purpura with underlying leukocytoclastic vasculitis
Pathogenesis of cryofibrinogenemia: precipitation of patients’ native fibrinogen or fibrin byproducts in (serum/plasma), but not in (serum/plasma)
Plasma
Serum
Most frequently associated disorders with secondary cryofibrinogenemia
Malignancy
Infections
Connective tissue disease
Autoimmune disease
The warm blood specimen should be anticoagulated with citrate, EDTA, or oxalate, but not _____, which nonspecifically precipitates fibrinogen and may result in a false positive result
Heparin
Histologic features of cryofibrinogenemia irrespective of the anatomic site
Occlusive thrombotic diathesis comprising eosinophilic refractile deposits within vessel lumina with extension into the vessel intima
Typical complications of cryofibrinogenemia due to thrombotic events
Gangrene
Septicemia
Leg amputation
Synthetic derivative of testosterone with substantial fibrinolytic properties
Has been effective for essential cryofibrinogenemia
Oral stanozolol (2-4 mg twice daily)
Has a more rapid onset of action than stanozolol
Streptokinase (sometimes in combination with streptodornase), given intravenously (25,000-200,000 U/d)
Other combination treatments for cryofibrinogenemia
Colchicine (0.6 mg twice daily) in combination with high-dose pentoxifylline (800 mg 3 times daily)
Combination of glucocorticoids (prednisone 10-60 mg/d) with low-dose aspirin, or other immunosuppressive agents (azathioprine 150 mg/d or chlorambucil 10 mg/d)
