Thromboembolic complications have been frequently reported in patients with long-lasting
nephrotic syndrome (NS).[1] Although thrombotic complications in the venous system
are common in patients with NS, arterial thromboses associated with NS are much less
common.[1] However, coronary thromboses are extremely rarely observed.[1],[2] So,
NS is a rare cause of acute coronary syndrome (ACS). As such, the incidence, pathogenesis,
and treatment of these patients have yet to be clearly defined. In the current literature,
publications contain less than 15 patients, most of whom are young children.[3]
Serious clotting factor disturbances can be observed, such as changes in platelet
hyperfunction, increased plasma fibrinogen, abnormalities of the fibrinolytic system,
and acquired deficiencies of coagulation inhibitors.[2] However, increased platelet
aggregation and antithrombin III (AT III) deficiency are the most important factors
in this hypercoagulable state in the NS.[4] A hypothesis for hypercoagulable state
in NS suggests a clinical correlation between thromboembolism and the underlying renal
disease (especially minimal change glomerulopathy).[1],[2],[5],[6] Patients with chronic
excess proteinuria and long-term exposure to abnormalities of hemostasis and lipid
profiles appear to have a high risk of developing cardiovascular disease.[4]
In our study, we evaluated the characteristics of eight patients admitted to our hospital
with a diagnosis of acute myocardial infarction (AMI) by ECG, clinical presentation
and myocardial enzyme. They were all diagnosed NS before AMI. To our knowledge, this
is the first study of multiple cases of NS associated with AMI.
In this case study, the cases presented here were retrospectively collected from a
database of Jinling Hospital in which who had AMI. From 1800 patients who had been
admitted to our Department for AMI, we found eight cases of combined NS. These patients
were enrolled in the study from 2008 through 2016. All patients were diagnosed with
NS and meanwhile AMI based on symptoms, electrocardiogram and myocardial enzyme. Follow-up
at one year was achieved in 62.5% patients.
Two of the patients were female (25%) and six of the patients were male. The age range
was between 29 and 72 years with a mean age of 55 years (54.5 years for men, 56.5
years for women). Seven patients (87.5%) are taking oral hormone therapy for a long
time. Patients with specific pathologic diagnosis were membranous nephropathy (MN)
while three of them have no data. The most infarcted area is inferior wall (62.5%).
Three patients died during hospitalization. Severe hypoalbuminemia and proteinuria
can be observed in most of the patients (Table 1).
Table 1.
Baseline clinical characteristics of patients.
Patients
1
2
3
4
5
6
7
8
Age, yrs
29
54
65
59
58
72
62
41
Gender
Male
Male
Male
Male
Male
Female
Male
Female
Hypertension
No
No
Yes
Yes
No
Yes
Yes
No
Diabetes
No
No
No
Yes
No
No
No
No
Dyslipidemia
Yes
No
No
No
No
No
No
No
Smoking
No
Yes
No
Yes
No
No
No
No
Previous heart disease
No
No
No
No
No
No
No
No
Troponin I, ng/L
ND
42.03
1.71
117.9
NA
NA
NA
50
Oral glucocorticoids treatment
Yes
Yes
Yes
Yes
Yes
Yes
No
Yes
Pathological diagnosis
ND
MN
MN
ND
MN
MN
MN
ND
Albumin, g/L
ND
25.8
30.8
18.1
19.8
33.3
25.9
16.1
Proteinuria
No
Yes
Yes
Yes
NA
Yes
Yes
Yes
The interval between the diagnosis and the onset of the disease
21 years
5 months
3 years
1 year
ND
6 years
2 years
1 months
Infarction area
Anterior wall+side wall
Anteroseptal+ high lateral wall
Inferior wall+back wall+right ventricle
Anterior wall
Inferior wall+high lateral wall+ back wall
Inferior wall
Inferior wall
Inferior wall
Hospital ending
Discharged
Discharged
Death
Discharged
Death
Discharged
Death
Discharged
Follow-up
No events
No events
ND
No events
ND
Death
ND
No events
MN: membranous nephropathy; NA: not available; ND: no data.
Three people had coronary angiography and stent implantation. Two patients were treated
with percutaneous transluminal coronary angioplasty (PTCA) only and two with thrombus
spiration or thrombolysis. The incidence of cardiogenic shock was 3/8 (37.5%). The
rate of no reflow or slow blood flow 3/8 (37.5%). In most patients, thrombosis is
seen in coronary angiography, rather than in coronary atherosclerosis. Some people
only do PTCA or thrombus and take the medicine in the coronary artery. The lesion
of the blood vessel is dominated by the left anterior descending (LAD) and the right
coronary artery (RCA). Most patients are found with either no reflow or slow blood
flow (Table 2).
Table 2.
Angiography characteristics.
Patients
1
2
3
4
5
6
7
8
Culprit vessel
LAD
LAD
RCA
LAD
ND
RCA
ND
RCA
Multi-vessel lesions
Yes
No
Yes
Yes
ND
Yes
ND
No
Severe calcification
No
No
Yes
No
ND
No
ND
No
Diffuse lesion
Yes
No
Yes
Yes
ND
Yes
ND
No
Treatment
PTCA
Thrombus spiration
PTCA
Stent
Thrombolysis
stent
ND
Stent+thrombus Spiration+PTCA
Number of stents
0
0
0
2
0
3
ND
1
Length of stents
ND
ND
ND
52 mm
ND
63 mm
ND
23 mm
Thrombus spiration
No
Yes
No
No
ND
No
ND
Yes
Cardiac shock
No
No
Yes
Yes
Yes
No
ND
No
No reflow or slow blood flow
No
Yes
Yes
No
ND
No
ND
Yes
Intravascular medicine
No
Yes
No
No
ND
No
ND
Yes
LAD: left anterior descending; ND: no data; PTCA: percutaneous transluminal coronary
angioplasty; RCA: right coronary artery.
The first report on coronary heart disease complicating NS was published 1969 by Berlyne
and Mallick, who described the occurrence of AMI in four patients with NS due to glomemlonephritis.
Now the combination of these diseases is still rare. Previous reports of such diseases
are mostly case reports, and are mostly about young people.
We presented a case series of AMI secondary to NS mostly due to MN. In our cases,
the age distribution is between 29 and 72 years old, It's interesting that the AMI
occurs in patients of NS at all ages, not only young people. We also summarized the
treatment of these patients. Most of the patients were treated with percutaneous coronary
intervention and recovered well.
Most patients with coronary angiography can see a thrombosis, which can be identified
as an acute coronary thrombosis, rather than an atheromatous plaque. In the treatment,
some patients had a PTCA and did not implant stent, and the blood clots were taken
from the blood clot. Coronary thrombosis can be seen in hypercoagulable states such
as in the antiphospholipid syndrome, NS, and factor XII and protein S deficiencies,
etc.[7]–[10] The possible pathogenesis of AMI in NS has been discussed in the former
study.[11] The underlying mechanisms of the “thrombophilia” of the NS are multiple
but seem related with an imbalance of prothrombotic factors. Firstly, factors associating
with coagulation are enhanced. The proteinuria associated with NS leads to the loss
of low molecular weight protein, such as factors IX, XI, and XII, as the liver tries
to compensate for the hypoalbuminaemic state, there is an increased synthesis of factors
II, VII, VIII, X, XIII, and fibrinogen.[12]–[14] Thrombocytosis and increased platelet
aggregation and adhesiveness also contribute to the hypercoagulable state. Platelet
hyperaggregability correlates with serum cholesterol concentrations. Secondly, factors
associating with anticoagulation are weakened. Antithrombin III, a coagulation inhibitor
significant reductions can be observed especially when the serum albumin concentration
is below 20 g/L.
However, protein C and protein S are coagulation inhibitors whose decline has not
been clearly implicated in arterial thrombosis in the NS. Thirdly, the imbalance of
fibrinolytic system, with decreased concentrations of plasminogen and raised levels
of plasminogen activator, contributes to the “thrombophilia”.[15] There is evidence
of decreased fibrinolytic activity with hypertriglyceridemia, which often occurs in
the NS.[16] And the extent of alterations in imbalance of prothrombotic factors correlate
with the degree of hypoalbuminaemia. A serum albumin of less than 25 g/L is a significant
risk factor for combined arterial and venous thrombosis in the NS.[17] Other factors
that contribute to the hypercoagulable state are a thrombocytosis and increased platelet
aggregation and adhesiveness. Platelet hyperaggregability correlates with serum cholesterol
concentrations.[18],[19] Many of these abnormalities were evident in our patient and
may have caused coronary thrombosis without atherosclerotic plaque rupture.
Most of our patients are MN, which is a glomerular disease characterized by NS and
typical changes on renal biopsy. Most patients present with a NS (80%). In the past,
MN was considered as a presentation of chronic serum sickness. With research evolvement,
MN like other glomerular diseases is now thought to be an autoimmune disease.[20]
Oral hormone therapy is considered beneficial in the medium risk group (normal plasma
creatinine, proteinuria between 4 and 8 g on a maximal conservative treatment).
In conclusion, the cases report indicates that AMI is probably due to arterial thrombosis
that can be attributed to a hypercoagulable state resulting from the NS, which may
be an independent risk factor of AMI. Although rare, AMI should be considered even
without traditional risk factors. A detailed clinical history may help to identify
the aetiology, and guide subsequent management, but diagnostic coronary angiography
is essential. Aspirin is recommended in most cases. Anticoagulation should be considered
in the NS if serum albumin is less than 20 g/L.[12] Careful risk factor modification
and treatment of the underlying cause should reduce the incidence of recurrent cardiac
events. In summary, NS is a rare cause of AMI. However, special attention should be
paid to the high coagulation state. And anticoagulation should be considered as a
prophylactic therapy.