- •
Thrombotic microangiopathies, including thrombotic thrombocytopenic purpura (TTP), HUS and HELLP and its cousins—ITP, HIT, and DIC—are serious conditions that the emergency physician must recognize early to initiate life-saving treatments.
- •
The diagnosis of TTP only requires evidence of a microangiopathic hemolytic anemia with thrombocytopenia and no other explanation.
- •
A high clinical suspicion for thrombotic microangiopathies should be maintained in any patient presenting with thrombocytopenia or
Thrombotic Microangiopathies (TTP, HUS, HELLP)
Section snippets
Key points
Thrombotic Thrombocytopenic Purpura
Thrombotic thrombocytopenic purpura (TTP) is a systemic disease characterized by platelet aggregation into widespread platelet thrombi and resulting occlusion of the body’s microvasculature. This disease is closely related to and overlaps with hemolytic uremic syndrome (HUS) within the broader definition of TMAs.5 Historically, TTP has had mortalities as high as 90% when left untreated.6 Prompt recognition and initiation of early therapy have drastically reduced that mortality rate to 10% to
Immune thrombocytopenia purpura (ITP)
ITP is an acquired immune-mediated syndrome characterized by an isolated thrombocytopenia and increased risk of bleeding. It is classified as primary ITP, a diagnosis of exclusion with no inciting cause, or secondary ITP, an underlying condition or medication drives the immunologic response leading to platelet degradation.
HELLP
HELLP is a life-threatening condition that presents in pregnancy after 20 weeks’ gestation. It is regarded as a severe variant of preeclampsia, which may or may not be known at the time of diagnosis. Patients diagnosed with HELLP earlier in pregnancy tend to have significantly worse symptoms and disease course. The unborn fetus can also be affected, particularly with earlier disease manifestations resulting in fetal growth restriction.
Disseminated intravascular coagulation (DIC)
DIC is an acquired, systemic process of overstimulation of the coagulation pathway resulting in thrombosis, followed by consumption of platelets and coagulation factors, and ending in hemorrhage. DIC can be acute and decompensated when the generation of clotting factor cannot match the excessive consumption, or chronic and compensated when the clotting factor consumption is matched by production. Acute DIC has a rapid onset with bleeding seen in more than 64% of cases.65 Bleeding from more than
HIT
HIT occurs after the initiation of heparin and is divided into 2 distinct processes. Type 1 is generally clinically benign, non-immune-mediated, and a direct medication mediated effect. On the other hand, type 2 is a life-threatening and limb-threatening immune-mediated process with the formation of antibodies against the heparin-platelet factor 4 complex (PF4).68 Patients are often asymptomatic with unexplained thrombocytopenia 4 to 10 days after heparin exposure. Spontaneous bleeding is
Summary
TMAs including TTP, HUS, HELLP and the related disease processes, ITP, HIT and DIC, are serious conditions that the EP must recognize early to initiate life-saving treatments. Although it may be challenging to make the diagnosis, a heightened awareness in the thrombocytopenic patient should trigger a diagnostic evaluation and consultation with a hematology specialist to ensure appropriate management and a safe disposition plan (Table 10).
References (70)
- et al.
The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia
Blood
(2011) - et al.
Heparin-induced thrombocytopenia: a contemporary clinical approach to diagnosis and management
Chest
(2009) - et al.
Thrombotic thrombocytopenic purpura: a hematological emergency
J Emerg Med
(2012) How I treat patients with thrombotic thrombocytopenic purpura: 2010
Blood
(2010)- et al.
Cardiac involvement in acute thrombotic thrombocytopenic purpura: association with troponin T and IgG antibodies to ADAMTS 13
J Thromb Haemost
(2009) - et al.
A phase 2 study of the safety and efficacy of rituximab with plasma exchange in acute acquired thrombotic thrombocytopenic purpura
Blood
(2011) - et al.
Thrombotic thrombocytopenic purpura in 166 pregnancies: 1955–2006
Am J Obstet Gynecol
(2008) - et al.
Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome in pregnancy: review of 11 cases
Am J Obstet Gynecol
(1996) - et al.
Shiga-toxin-producing Escherichia coli and hemolytic uremic syndrome
Lancet
(2005) Untying the knot of thrombotic thrombocytopenic purpura and atypical hemolytic uremic syndrome
Am J Med
(2013)
Thrombotic microangiopathies: the past as prologue
Eur J Intern Med
Prevalence of immune thrombocytopenia: analyses of administrative data
J Thromb Haemost
High risk of severe bleeding in aged patients with chronic idiopathic thrombocytopenic purpura
Blood
Immune Thrombocytopenia
Hematol Oncol Clin North Am
Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group
Blood
Therapy with high-dose dexamethasone in previously untreated patients affected by idiopathic thrombocytopenia purpura: a GIMEMA experience
Blood
Childhood immune thrombocytopenic purpura: diagnosis and management
Hematol Oncol Clin North Am
A prospective comparative study of 2540 infants and children with newly diagnosed idiopathic thrombocytopenia purpura (ITP) from the Intercontinental Childhood ITP Study Group
J Pediatr
Severe hemorrhage in children with newly diagnosed immune thrombocytopenic purpura
Blood
Severe pre-eclampsia and hypertensive crises
Best Pract Res Clin Obstet Gynaecol
Pathogenesis of the syndrome of hemolysis, elevated liver enzymes, and low platelet count (HELLP): a review
Eur J Obstet Gynecol Reprod Biol
Syndrome of hemolysis, elevated liver enzymes, and low platelet count: a severe consequence of hypertension in pregnancy
Am J Obstet Gynecol
Gastrointestinal and liver disease in pregnancy
Best Pract Res Clin Obstet Gynaecol
Hematologic complications of pregnancy
Semin Hematol
Heparin-induced thrombocytopenia: recognition, treatment, and prevention: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy
Chest
Thrombocytopenia
Intravascular and total body platelet equilibrium in healthy volunteers and in thrombocytopenic patients transfused with single donor platelets
Am J Hematol
Thrombotic microangiopathies
N Engl J Med
Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura
N Engl J Med
Guidelines on the diagnosis and management of the thrombotic microangiopathic hemolytic anemias
Br J Hematol
Guidelines on the diagnosis and management of thrombotic thrombocytopenic purpura and other thrombotic microangiopathies
Br J Hematol
Interventions for hemolytic uremic syndrome and thrombotic thrombocytopenic purpura
Cochrane Database Syst Rev
Current management and therapeutical perspectives in thrombotic thrombocytopenic purpura
Presse Med
Thrombotic thrombocytopenic purpura. Report of 25 cases and review of the literature
Medicine
Antibodies to von-Willebrand factor-cleaving protease in acute thrombotic thrombocytopenic purpura
N Engl J Med
Cited by (0)
Disclosure Statement: The authors have nothing to disclose.