Microangiopathic hemolytic anemia

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Mydah Sajid, MD [2]

Synonyms and keywords: Microangiopathic haemolytic anaemia; MHA

Overview

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

In medicine (hematology) microangiopathic hemolytic anemia (MAHA) is a subgroup of hemolytic anemia (anemia, loss of red blood cells through destruction) caused by factors in the small blood vessels. It is identified by the finding of anemia and schistocytes onmicroscopy of the blood film.

References

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Historical Perspective

The “microangiopathic hemolytic anemia” term was first coined by Symmers, a British physician in 1952. He described 33 patients presenting with constellation of symptoms of varying severity. The symptoms included fever, hemolytic anemia, thrombocytopenia and neurological deterioration^[1]. The neurological symptoms usually present at the latter course of the disease.

References

↑ SYMMERS WS (1952). “Thrombotic microangiopathic haemolytic anaemia (thrombotic microangiopathy)”. Br Med J. 2 (4790): 897–903. doi:10.1136/bmj.2.4790.897. PMC 2021829. PMID 12978378.

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Classification

Mydah Sajid, MD [1]

Classification

Microangiopathic hemolytic anemia may be classified into primary subtype based on the genetic mutations and no known underlying disease and secondary subtype due to known underlying cause^[1].

Primary:
- Thrombotic thrombocytopenic purpura
  - Congenital
  - Acquired
- Hemolytic Uremic Syndrome
  - Shiga toxin E-coli
  - Atypical

Secondary:
- Malignant hypertension
- Pregnancy
  - Pre-eclampsia, Eclampsia
  - Thrombotic microangiopathy
  - Hemolysis, elevated liver enzymes, low platelet count (HELLP syndrome)
- Drug or toxin mediated:
  - calcineurin inhibitors, quinine
- Viral infections:
- Cancer
- Disseminated intravascular coagulation
- Solid organ or bone marrow transplantation
- Nutritional deficiency: Vitamin B12 or vitamin C deficiency

References

↑ Arnold DM, Patriquin CJ, Nazy I (2017). “Thrombotic microangiopathies: a general approach to diagnosis and management”. CMAJ. 189 (4): E153–E159. doi:10.1503/cmaj.160142. PMC 5266569. PMID 27754896.

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Pathophysiology

Associate Editor(s)-in-Chief: Mydah Sajid, MD [1]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]

Overview

Pathophysiology

It is thought that microangiopathic hemolytic anemia is mediated by endothelial injury, platelet activation, microthrombi formation, intra-vascular hemolysis and thrombocytopenia.
In diseases such as hemolytic uremic syndrome, disseminated intravascular coagulation, thrombotic thrombocytopenic purpura, as well as malignant hypertension, the endothelial layer of small vessels are damaged with resulting fibrin deposition and platelet aggregation.
The mechanism of endothelial injury varies depending on the underlying cause. It results in platelets aggregation and activation the coagulation cascade. There is the formation of a fibrin mesh due to increased activity of coagulation cascade.
This results in the formation of microthrombi in the [[blood vessel] and reduction of the caliber of the blood vessels.
The red blood cells are fragmented due to mechanical sheering by the microthrombi.

Microscopic Pathology

The red blood cells are physically cut by these protein networks, and the fragments are identical to the schistocytes seen on light microscopy.

References

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Causes

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Mydah Sajid, MD [2]

Overview

Microangiopathic hemolytic anemia is a clinical manifestation of a large number of diseases. The gentic mutations make some patients prone to microangiopathic hemolytic anemia.

Causes

The most important causes are^[1]:

Aortic Stenosis (most common cause of MAHA)
Thrombotic thrombocytopenic purpura (TTP)
Hemolytic uremic syndrome (HUS)
Disseminated intravascular coagulation (DIC)
Drug Side Effect- Cyclosporine
HELLP syndrome and eclampsia
Heparin-induced thrombocytopenia (HIT)
Severe glomerulonephritis
Several other rare causes

References

↑ Kottke-Marchant K (2017). “Diagnostic approach to microangiopathic hemolytic disorders”. Int J Lab Hematol. 39 Suppl 1: 69–75. doi:10.1111/ijlh.12671. PMID 28447417.

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Differentiating Microangiopathic hemolytic anemia from other Diseases

Associate Editor(s)-in-Chief: Mydah Sajid, MD [1]

Microangiopathic hemolytic anemia must be differentiated from following diseases^[1]:


Disease	Findings
Pseudo-TTP (Vitamin B12 deficiency)	Patients have neurological symptoms like numbness, ataxic gait and tingling along with macrocytic anemia. There is a reduced level of reticulocytes, with elevated levels of Lactate dehydrogenase (i.e. greater than 5000 U/L), methylmalonate, and homocysteine.
Pregnancy induced fatty liver	Patients presents with right upper quadrant or epigastric abdominal pain, nausea and vomiting. On laboratory work-up, there is hypoglycemia along with deranged liver function tests. There is elevated levels of bilirubin, alanine aminotransferase, aspartate aminotransferase, reduced antithrombin III and coagulation factors level^[2].
Disseminated intravascular coagulation	Can occur in sepsis, and different malignancies like prostate cancer, Acute promyelocytic leukemia and Gastric cancer, there in increased consumption of fibrin. On laboratory work-up, there is reduced fibrinogen level, Auer rod in Acute promyelocytic leukemia and leukoerythroblastic picture, with nucleated [[red blood cell]s, poikilocytosis, left shift of white blood cells. In sepsis, there is elevation of procalcitonin along with positive blood culture and reduced levels of coagulation factors.
Endocarditis	Patients have multi-system involvement presenting with fever, sepsis, polyartharalgia, Janeway lesion, Osler’s node, and a new-onset or changed heart murmur. It is diagnosed clinically by Duke’s criteria. It is confirmed by blood culture and trans-esophageal echocardiography.
Evan’s syndrome	Immune mediated thrombocytopenia and autoimmune hemolytic anemia. Coombs test positive. On peripheral blood smear, there are no schistocytes.
Antiphospholipid syndrome	Women have a history of artery thrombi and deep venous thrombosis in lower extremeties, recurrent abortion, stroke and headache. These patients have prolonged activated partial thromboplastin time and positive serology for anti-cardiolipin antibodies.
Malaria, Babesiosis	Patients presents with periodic spikes of high-grade fever with rigors, chills, nausea, vomiting, fatigue, myalgia and malaise. The intra-cellular parasite are identified on special stained peripheral blood smear.
Viral Infections	In specific viral diseases like Dengue hemorrhagic fever, hantavirus and filoviridae, there is significant thrombocytopenia. Patients have a recent history of travel. There are no signs of hemolysis on laboratory workup.

References

↑ Bommer M, Wölfle-Guter M, Bohl S, Kuchenbauer F (2018). “The Differential Diagnosis and Treatment of Thrombotic Microangiopathies”. Dtsch Arztebl Int. 115 (19): 327–334. doi:10.3238/arztebl.2018.0327. PMC 5997890. PMID 29875054.
↑ Ko H, Yoshida EM (2006). “Acute fatty liver of pregnancy”. Can J Gastroenterol. 20 (1): 25–30. doi:10.1155/2006/638131. PMC 2538964. PMID 16432556.

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Epidemiology and Demographics

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Risk Factors

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Screening

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Natural History, Complications and Prognosis

If left untreated, 90% of patients with [[[microangiopathic hemolytic anemia]] may die^[1].
The prognosis can be improved with prompt treatment. Therapeutic plasmapheresis reduces mortality rate to 20%^[1].
Common complications of microangiopathic hemolytic anemia include^[2]:
- acute renal failure with raised serum urea and creatinine levels
- intracranial hemorrhage as a consequence of severe thrombocytopenia
- myocardial infarction due to coronary artery occlusion

Reference

↑ ^1.0 ^1.1 Rock GA, Shumak KH, Buskard NA, Blanchette VS, Kelton JG, Nair RC; et al. (1991). “Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura. Canadian Apheresis Study Group”. N Engl J Med. 325 (6): 393–7. doi:10.1056/NEJM199108083250604. PMID 2062330.
↑ Scully, Marie; Hunt, Beverley J.; Benjamin, Sylvia; Liesner, Ri; Rose, Peter; Peyvandi, Flora; Cheung, Betty; Machin, Samuel J. (2012). “Guidelines on the diagnosis and management of thrombotic thrombocytopenic purpura and other thrombotic microangiopathies”. British Journal of Haematology. 158 (3): 323–335. doi:10.1111/j.1365-2141.2012.09167.x. ISSN 0007-1048.

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Diagnosis

Treatment

Case Studies

Case#1

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Template:WikiDoc Sources

[pmid12978378-1] SYMMERS WS (1952). “Thrombotic microangiopathic haemolytic anaemia (thrombotic microangiopathy)”. Br Med J. 2 (4790): 897–903. doi:10.1136/bmj.2.4790.897. PMC 2021829. PMID 12978378.

[pmid27754896-1] Arnold DM, Patriquin CJ, Nazy I (2017). “Thrombotic microangiopathies: a general approach to diagnosis and management”. CMAJ. 189 (4): E153–E159. doi:10.1503/cmaj.160142. PMC 5266569. PMID 27754896.

[pmid28447417-1] Kottke-Marchant K (2017). “Diagnostic approach to microangiopathic hemolytic disorders”. Int J Lab Hematol. 39 Suppl 1: 69–75. doi:10.1111/ijlh.12671. PMID 28447417.

[pmid29875054-1] Bommer M, Wölfle-Guter M, Bohl S, Kuchenbauer F (2018). “The Differential Diagnosis and Treatment of Thrombotic Microangiopathies”. Dtsch Arztebl Int. 115 (19): 327–334. doi:10.3238/arztebl.2018.0327. PMC 5997890. PMID 29875054.

[pmid16432556-2] Ko H, Yoshida EM (2006). “Acute fatty liver of pregnancy”. Can J Gastroenterol. 20 (1): 25–30. doi:10.1155/2006/638131. PMC 2538964. PMID 16432556.

[pmid2062330-1] 1.0 ^1.1 Rock GA, Shumak KH, Buskard NA, Blanchette VS, Kelton JG, Nair RC; et al. (1991). “Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura. Canadian Apheresis Study Group”. N Engl J Med. 325 (6): 393–7. doi:10.1056/NEJM199108083250604. PMID 2062330.

[ScullyHunt2012-2] Scully, Marie; Hunt, Beverley J.; Benjamin, Sylvia; Liesner, Ri; Rose, Peter; Peyvandi, Flora; Cheung, Betty; Machin, Samuel J. (2012). “Guidelines on the diagnosis and management of thrombotic thrombocytopenic purpura and other thrombotic microangiopathies”. British Journal of Haematology. 158 (3): 323–335. doi:10.1111/j.1365-2141.2012.09167.x. ISSN 0007-1048.

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Microangiopathic hemolytic anemia

Overview

References

References

Classification

References

Overview

Pathophysiology

Microscopic Pathology

References

Overview

Causes

References

References

References

References

References

Reference

Diagnosis

Treatment

Case Studies

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