Question 7

Compare and contrast catastrophic antiphospholipid syndrome (APL), acute disseminated intravascular coagulation (DIC), and the thrombotic microangiopathies (TTP/HUS) under the following headings.

a)    Pathophysiology    (30% marks)

b)    Clinical presentation    (30% marks)

c)    Diagnostic laboratory features    (20% marks)

d)    Specific management    (20% marks)
 

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College answer

Not available.

Discussion

This SAQ brings together material previously explored in individual questions asking about disseminated intravascular coagulation antiphospholipid syndrome and thrombotic thrombocytopenic purpura. It is great to see that the examiners have produced clear expectations in the stem and pointed to the structure they prefer, but this is nothing to celebrate, as it really seems like some sort of bare minimum in assessment design. Moreover, considering the breadth of the subject matter, this question could have been a massive time sink. Consider: three syndromes, with four aspects, multiplies into twelve fields to fill for a full mark question, which means only about fifty seconds to write in each. Considering that even the fastest hand writers in the world can produce only about 28 words per minute, the maximum word count for each field is 23 words, and to explain the pathophysiology of TTP/HUS within this wordcount could not possibly have produced a winning answer.  To help the exam candidate, what follows is a table where some effort was taken to minimise and abbreviate everything as much as possible.

APLS DIC TTP/HUS
Pathophysiology
Antiphospholipid antibodies inhibit clotting, activate complement, activate immune cells, cause endothelial dysfunction. Net result is simultaneously anticoagulation and prothrombotic tendency. Inflammatory cytokines cause widespread endothelial dysfunction and activate platelet aggregation systemically, depleting fibrinogen, clotting factors and platelets ADAMTS-13 normally cleaves the prothrombotic factor vWF. Inflammatory endothelial activation in the presence of low ADAMTS-13 levels causes accumulation of large vWF multimers, causing microvascular thrombosis and haemolysis
Clinical presentation
Thrombosis (eg. cerebral venous or arterial), DVT, PE, miscarriage,  thrombocytopenia, microvascular occlusion/infarction leading to multiorgan dysfunction

Thrombocytopenia, coagulopathy, hypofibrinogenaemia, petechii, multiorgan dysfunction, concomitant sepsis or other cause of SIRS

Anaemia, thrombocytopenia, 

decreased LOC, 

fever and renal failure, purpura rash, raised LDH,
MAHA-like blood film

Diagnostic laboratory features
Lupus anticoagulant,
anti-β2-glycoprotein-I antibodies
Fibrinogen depletion, extremely high D-dimers, thrombocytopenia,
raised INR, 

Low ADAMTS-13 level;

thrombocytopenia

Specific management
Anticoagulation (heparin) with anti-Xa monitoring, steroids, plasmapheresis, IVIG, cyclophosphamide, rituximab. Treating the cause; avoidance of exogenous clotting factors;
activated protein C, tifacogin or thrombomodulin are experimental
Plasmapheresis, with FFP replacement.

References

Garcia, David, and Doruk Erkan. "Diagnosis and management of the antiphospholipid syndrome." New England Journal of Medicine 378.21 (2018): 2010-2021.

Cervera, Ricard. "Antiphospholipid syndrome." Thrombosis research 151 (2017): S43-S47.

Boral, Benjamin M., Dennis J. Williams, and Leonard I. Boral. "Disseminated intravascular coagulation." American journal of clinical pathology 146.6 (2016): 670-680.

Slofstra, Sjoukje, Arnold Spek, and Hugo ten Cate. "Disseminated intravascular coagulation." The Hematology Journal 4.1 (2013): 295-30

George, James N. "Thrombotic thrombocytopenic purpura." New England Journal of Medicine 354.18 (2006): 1927-1935.