Chapter 24 - Cutaneous Manifestations of Microvascular Occlusion Syndromes

Question 1

Antibodies to which antigen cause heparin-induced thrombocytopenia?

Answer 1

Antibodies to complexes of heparin and platelet factor 4

Question 2

True or false: patients with heparin-induced thrombocytopenia (HIT) will always develop HIT with future heparin exposures.

Answer 2

False; if the patient is exposed to heparin again 100 days or more after the initial episode of HIT, the antibodies necessary to produce this reaction may not be prodcued again, and a second episode of HIT may not occur

Question 3

Are the platelet plugs that form in heparin-induced thrombocytopenia (HIT) inflammatory or non-inflammatory?

Answer 3

Non-inflammatory

Question 4

True or false: a normal platelet count excludes the diagnosis of heparin-induced thrombocytopenia (HIT).

Answer 4

False; there is typically a drop in the platelet count, however, sometimes if the pre-heparin platelet count isn’t known, the drop will produced a platelet count that is still within the normal range

Question 5

Both unfractionated and fractionated heparin can produce heparin-induced thrombocytopenia (HIT). Which type produces HIT more often?

Answer 5

Unfractionated heparin

Question 6

Why is starting warfarin during an episode of heparin-induced thrombocytopenia (HIT) unwise?

Answer 6

Because thrombosis may be potentiated by a drop in protein C levels (this always occurs when starting warfarin, hence the typical “heparin bridging” used during the first few days of warfarin therapy)

Question 7

What are the two myeloproliferative disorders that typically produce platelet-induced occlusion of blood vessels?

Answer 7

Essential thrombocythemia and polycythemia vera

Question 8

What is the name of the condition that’s characterized by burning and paroxysmal erythema of the distal extremities, frequently triggered by skin contact with a warm surface?

Answer 8

Erythromelalgia

*Note: erythromelagia can be primary (idiopathic) or secondary.

Question 9

Is secondary erythromelalgia more closely associated with essential thrombocythemia or polycythemia vera?

Answer 9

Essential thrombocythemia

Question 10

What comprises a “white clot” seen on histologic exam within a blood vessel?

Answer 10

Platelets (however, even the most experienced pathologist may have difficulty distinguishing a “white clot” from a fibrin clot)

Question 11

What type of mutation do 90-95% of patients with polycythemia vera and 50-70% of patients with essential thrombocythemia have?

Answer 11

JAK-2 mutation

Question 12

What drug can be used to effectively treat the erythromelalgia caused by thrombocythemia?

Answer 12

Aspirin

Question 13

What’s the name of the condition in which there may be cytopenia of any, or all, blood components, and yet patients have an increased risk of thrombosis due to platelet occulsion? The patients can develop retiform purpura, and they have hemolytic anemia that is Coombs negative.

Answer 13

Paroxysmal nocturnal hemoglobinuria

Question 14

What does the purpura look like in hemolytic uremic syndrome (HUS)?

Answer 14

There is no purpura; this is a finding associated with full-blown thrombotic thrombocytopenic purpura (TTP) syndrome only

Question 15

What’s the difference between plasma and serum?

Answer 15

Plasma contains fibrinogen and clotting factors, while serum doesn’t

Question 16

Will cryofibrinogens be found in serum, plasma, or both?

Answer 16

Cryofibrinogen will only be found in plasma, since serum doesn’t contain any fibrinogen

Question 17

Will cryoglubulins (immunoglobins that precipitate when exposed to the cold) be found in serum, plasma, or both?

Answer 17

Both

Question 18

Through what two mechanisms can cryoglubuins cause disease?

Answer 18

Through occlusion or immune complex vasculitis

Question 19

Name this phenomenon: a clinical presentation that occurs exclusively in leprosy patients from Mexico and Central America, where recurrent crops of large ulcers form on the lower extremities.

Answer 19

Lucio’s phenomenon

Question 20

Warfarin blue toe syndrome is also known as:

Answer 20

Cholesterol emboli (warfarin, or a different anti-coagulant, gradually lyses the clot overlying a plaque, leaving it subject to the shear stress of arterial flow)

Question 21

What diagnosis should be considered in a patient with renal failure and a history of recurrent nephrolithiasis, who presents with acute retiform purpura?

Answer 21

Oxalate embolus

Question 22

What is the term that describes widespread purpura in septic patients?

Answer 22

Purpura fulminans

Question 23

What population is at greatest risk for post-infectious purpura fulminas?

Answer 23

Children

Question 24

What two microbes most commonly cause post-infectious purpura fulminans in children (i.e. purpura fulminans two weeks after the onset of the infection)?

Answer 24

Group A streptococcus and VZV infections

Question 25

What do antibodies bind to in the pathogenesis of heparin necrosis?

Answer 25

Platelet factor 4 + heparin complexes

Question 26

What alternate anticoagulant agents are options in the setting of heparin necrosis?

Answer 26

LMWH, argatroban, danaparoid, lepirudin

Question 27

What bloodwork would you order in microvascular occlusion syndromes?

Answer 27

CBCd, smear, PTT, cryoglobulin, LFTs, Cr, BUN, ANCA, skin biopsy

Question 28

What myeloproliferative disorders are the most likely to cause platelet plugging occlusions?

Answer 28

Essential thrombocythemia, polycythemia vera

Question 29

What are platelet plugs traditionally referred to as on histology?

Answer 29

“White clot”

Question 30

What is the mutation in paroxysmal nocturnal hemoglobinuria?

Answer 30

Phosphatidyl inositol glycan class A (PIG-A)

Question 31

What abN bloodwork would you find in those with TTP?

Answer 31

Thrombocytopenia, microangiopathic hemolytic anemia, renal disease, NORMAL PTT

Question 32

Describe the 3 types of cryoglobulins.

Answer 32

Type I) monoclonal, IgG, IgM; type II) mixed monoclonal Ab, IgM binds to polyclonal IgG; type III) mixed polyclonal. Both types II and III have RF properties and is known as ‘essential mixed cryolobulinemia’.

Question 33

What are the difference between Lucio’s phenomenon and erythema nodosum leprosum?

Answer 33

LP has no fever, leukocytosis or tenderness; it also responds poorly to thalidomide and is associated with diffuse lepromatous leprosy

Question 34

What type of biopsies do you want for query cholesterol embolization?

Answer 34

1) punch bx of retiform purpura 2) elliptical incision around blanched part of livedo reticularis