Performance of MCMDM-1vWD Questionnaire for Bleeding in Saudi Patients with Coagulation Factors Deficiency

Abstract

Citation: Khalid A AlSaleh (2021) Performance of MCMDM-1vWD Questionnaire for Bleeding in Saudi Patients with Co-agulation Factors Deficiency. J Cardio Vasc Med 7: 1-15. Abstract Background: Coagulation factors entail a critical pathway in clot formation, and inherited deficiencies in any of these

Full text

JScholar Publishers
Performance of MCMDM-1vWD Questionnaire for Bleeding in Saudi Patients with
Coagulation Factors Deciency
Khalid A AlSaleh1, Nouf Al-Numair2, Ayman AlSuliman3, Mohammed Zolaly4, Ahmad Tarawih5, Faisal AlZahrani6, Fais-
al AlAllaf7, Abdulkareem AlMomen8 and Tarek Owaidah9,10*
1Department of Medicine, College of Medicine, King Saud University, Riyadh, KSA, Saudi Arabia
2Department of Genetics, King Faisal Specialist Hospital and Research Centre, and College of Medicine, Alfaisal University,
Riyadh, KSA, Saudi Arabia
3Research center, King Faisal Specialist Hospital, Alfaisal University, Riyadh, KSA. asulaiman@kfshrc.edu.sa
4Department of Pediatrics, Taibah University, Medina, KSA, Saudi Arabia
5Medina Maternity and Children Hospital, Medina, KSA, Saudi Arabia
6Department of Pathology, Imam Abdulrahman Bin Faisal University, Dammam, KSA. fmzahrani@iau.edu.sa
7Department of Molecular Medicine, Umm alQura University, Makkah, KSA, Saudi Arabia
8Department of Pathology, College of Medicine, King Saud University, Riyadh, KSA, Saudi Arabia
9Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, KSA, Saudi
Arabia
10Alfaisal University, Riyadh, KSA, Saudi Arabia
Journal of
Cardiology and Vascular Medicine
Citation: Khalid A AlSaleh (2021) Performance of MCMDM-1vWD Questionnaire for Bleeding in Saudi Patients with Co-
agulation Factors Deciency. J Cardio Vasc Med 7: 1-15.
Received Date: June 06, 2021 Accepted Date: July 06, 2021 Published Date: July 08, 2021
*Corresponding author: Tarek Owaidah, Professor of Hematology and Transfusion Medicine, Alfaisal University, King
Faisal Specialist Hospital, Centre of excellence in thrombosis and Hemostasis, PO Box: 3354, Riyadh 11211, KSA, Saudi
Arabia, Tel: +966 50 531 2925, E-mail: towaidah@kfshrc.edu.sa
©2021 e Authors. Published by the JScholar under the terms of the Crea-
tive Commons Attribution License http://creativecommons.org/licenses/
by/3.0/, which permits unrestricted use, provided the original author and
source are credited.
J Cardio Vasc Med 2021 | Vol 7: 202
Open AccessResearch Article
Abstract
Background: Coagulation factors entail a critical pathway in clot formation, and inherited deciencies in any of these
factors lead to a heterogeneous group of bleeding disorders. e current study aimed to nd a correlation between bleeding
symptoms and factor deciency in Saudi Arabia.
Methods: Young Saudi adults with bleeding symptoms were questioned using a semistructured validated condensed MC-
MDM-1vWD questionnaire, and were tested for Prothrombin Time, activated partial thromboplastin time, and dierent
coagulation factor levels. Aer testing, only those participants whose factor deciencies were conrmed were selected for
further analysis.

2
JScholar Publishers
J Cardio Vasc Med 2021 | Vol 7: 202
Introduction
Bleeding disorders are a group of heterogeneous, gener-
ally inherited conditions which are characterized by hemostasis
abnormalities due to deciencies in coagulation factors, leading
to extended or spontaneous bleeding episodes [1,2]. e severity
and frequency of these episodes depends on the specic coag-
ulation factor deciency. Hemophilia A and B, along with von
Willebrand disease (vWBD) comprise of 95–97% of all bleed-
ing disorders and are caused by deciencies of factor VIII, factor
IX and von Willebrand factor, respectively. All other disorders,
called Rare blood disorders (RBDs), comprise the rest 3-5% of
bleeding disorders [1]. Even though RBDs are prevalent in all
populations, their incidence is higher in populations where con-
sanguineous marriages are common and are caused due to fac-
tors (F) I, II, V, VII, X, XI or XIII deciencies [3].
Distinct and robust diagnostic criteria for severe bleed-
ing disorders are present in healthcare settings, but the diagno-
sis of mild bleeding disorders (MBDs) remains a challenge. As
many as over 20% of the general population report at least one
bleeding symptom [4] which leads to both over- and underdiag-
nosis of MBDs. Even though mild forms of bleeding disorders
are not life-threatening, a correct diagnosis is essential to prevent
and prepare for bleeding episodes during hemostatic challenges
[4,5].
Occurrence of bleeding symptoms in otherwise healthy
individuals is an indication of a possible underlying MBDs in
many cases [3]. Over the years, several attempts have been made
to standardize tools for diagnosing blood disorders with a his-
tory of bleeding symptoms in patients [6]. Common bleeding
symptoms used for standardization include epistaxis, cutaneous
symptoms, bleeding from minor wounds, oral bleeding, gastro-
intestinal bleeding, surgery, muscle/hemarthrosis, and menor-
rhagia [7]. Currently, a concise bleeding symptom questionnaire
called condensed MCMDM-1vWD is being used to identify not
only severe and common, but also mild bleeding disorders [5].
Along with MCMDM-1VWD, bloodcoagulation tests are also
performed to conrm MBD diagnosis. In this regard, the most
commonly used diagnostic assays are prothrombin time (PT)
and activated partial thromboplastin time (APTT). Most of the
rare bleeding disorders don’t depend on them, though, and re-
quire factor level assay [8].
e current study is aimed to evaluate the performance
of MCMDM-1vWD as a tool for correctly detecting bleeding
persons with MBD in the Saudi population.
Methods
Institutional Review Board (IRB) approval was obtained
from King Faisal Specialist Hospital, Riyadh, with a multicenter
amendment achieved later on. A large epidemiological study was
conducted aer a random selection of young Saudi adults of both
genders in dierent parts of the country. e survey was carried
out in four major cities of Saudi Arabia, i.e., Makkah, Madinah,
Dammam, and Riyadh. A semistructured and abridged version
of MCMDM-1vWD questionnaire was used for this survey. e
questionnaire was used due to its proven objectivity and quanti-
ability for bleeding disorders. e questionnaire was translated
Results: GI bleeding and factor V were signicantly co-related (P-value 0.019, Fisher exact 0.028). Out of 48 respondents
with normal factor (F)V, 10.4% had GI bleeding symptoms, while out of 17 respondents with F-V deciency, 35.3% had GI
bleeding symptoms. Surgery and F-V were also signicantly related (P-value 0.011, Fisher exact 0.017). Out of 48 respondents
with normal F-V, 12.5% had bleeding during surgery, while out of 17 respondents with F-V deciency, 41.2% had bleeding
during surgery. We found no signicant relationship between any other coagulation factor deciency and bleeding responses,
while epistaxis, oral bleeding, and surgery were signicantly related to prolonged Prothrombin Time (PT); (P–value 0.02),
(P–value 0.012), (P–value 0.039), respectively. Cutaneous bleeding, bleeding from minor wounds, and menorrhagia were sig-
nicantly related to prolonged Activated Prothrombin Time (APTT); (P–value <0.0001), (P–value 0.038), (P–value <0.0001),
respectively.
Conclusion: e current study signies the correlation of mild bleeding symptoms with factor deciency and highlights
the higher prevalence of factor deciencies which may need larger national surveys to increase the statistical power of such
associations for better management of these patients.
Keywords: Inherited; Bleeding; Coagulation; Questionnaire

JScholar Publishers
J Cardio Vasc Med 2021 | Vol 7: 202
3
in Arabic for practicality purposes, and the translation was val-
idated while the survey was conducted by trained interviewers
uent in Arabic [5,9].
Questions and subquestions asked were about bleeding
symptoms, as well as about clotting factor deciencies. Ques-
tions about bleeding symptoms pertained to: 1) Epistaxis, 2)
Cutaneous Symptoms, 3) Bleeding from minor wounds, 4) Oral
bleeding, 5) Gastrointestinal bleeding, 6) Surgery, 7) Muscle/
hemarthrosis, and 8) Menorrhagia. e candidates were to an-
swer 1) Yes or 2) No in response to these questions in accordance
with their symptoms.
On the other hand, tests were performed to detect de-
ciencies for factors II, V, VII, VIII, IX, X, XI, and XIII, while
Factor XII was not considered in this study because it is not com-
monly related with bleeding events.
Only those participants who answered positively to one
of the primary questions were sampled for blood coagulation. All
tests were performed at Centre of Excellence in rombosis and
Hemostasis (CETH), Riyadh. Blood samples were collected in 10
cc sodium citrate (3.2%), 10 cc EDTA, and 5 cc sodium heparin
tubes to carry out various coagulation tests. All coagulation tests,
including prothrombin time (PT), activated prothrombin time
(APTT), and all factor assays were performed using reagents
from Stago, and STAR Max® Diagnostica Stago instrument at
CETH. All samples were processed in 2–4 hours of collection.
Plasma separation was performed by centrifugation, and frozen
samples were then transported to CETH for coagulation test-
ing. For ecient testing, those with only prolonged PT (normal
range: 11–14.5 seconds) were tested for the extrinsic pathways
(Factors II, V, VII and X), while those with only prolonged APTT
(normal range: 26–40 seconds) were tested for the intrinsic path-
ways (Factors VIII, IX, XI).
Only those participants whose factor deciencies were
conrmed aer coagulation testing were selected for further
analysis. Bleeding symptoms of participants with factor de-
ciency were examined, and statistical analysis was performed to
determine if any correlation were present between the bleeding
symptoms of participants and their coagulation factor deciency.
Our objective was to compare bleeding questionnaire
response with coagulation factor, PT and APTT related values.
Bleeding Assessment Tool
A bleeding assessment tool (BAT) for bleeding symp-
toms was used with coagulation factor deciency of <50% (10).
From the patient data, a symptom-specic score was generated
for each bleeding symptom. We assigned the score according to
the grading criteria depicted in Table 1, which was devised by the
study steering committee and not available to the eld physician.
Finally, we summed up all symptom scores to achieve the nal
score.
Symptoms Score
0 1 2 3
Epistaxis Trivial or < 5 Episode > 5 Consultation -
Cutaneous Trivial or < 5 Episode > 5 Consultation -
Bleeding from minor wounds Trivial or <5 Episode > 5 Consultation -
Oral Bleeding Trivial or <5 Episode > 5 Consultation -
GI Bleeding Trivial or <5 - Consultation -
Surgery Trivial or no bleeding Surgical bleeding episode Consultation Surgical hemostasis
Muscle/hemarthrosis Trivial or <5 Episode > 5 Consultation Compression
Menorrhagia Trivial or <5 Episode > 5 Consultation Medication
Table 1: Scoring criteria for the bleeding symptoms
Statistical Analysis
Descriptive statistics were computed for the categorical
variables using frequency and percentages. Continuous variables
were converted to categorical using normal ranges as criteria.
Fishers Exact test was run to assess the signicance between
categorical variables related to the questionnaire and clotting
factors. Odds ratios were computed between clotting factor and
questionnaire, while ROC was computed between clotting factor
and bleeding score. We used the soware STATA v.13.0 (Stata
Corp., College Station, TX, USA) in our analysis. A statistical
signicance threshold of P<0.05 was adopted.
Results
Out of 1,138 volunteering young adults in the initial
survey, coagulation factor data were available for only 194 re-
spondents.

JScholar Publishers
J Cardio Vasc Med 2021 | Vol 7: 202
4
Epistaxis
FVIII normal FVIII decient Fischer’s
No (60.3) 97 (40.0) 2 0.322
Yes (39.7) 64 (60.0) 3
FII normal FII decient Fischer’s
No (59.3) 35 (50.0) 1 0.656
Yes (40.7) 24 (50.0) 1
FV normal FV decient Fischer’s
No (60.4) 29 (58.8) 10 0.565
Yes (39.6) 19 (41.2) 7
FVII normal FVII decient Fischer’s
No (60.3) 38 (50.0) 1 0.644
Yes (39.7) 25 (50.0) 1
FIX normal FIX decient Fischer’s
No (61.6) 82 (60.0) 3 0.639
Yes (38.4) 51 (40.0) 2
FXIII normal FXIII decient Fischer’s
No (53.7) 22 -
Yes (46.3) 19 -
FX normal FX decient Fischer’s
No (60.0) 33 0 0.411
Yes (40.0) 22 (100) 1
vWF Ag normal vwfAg decient Fischer’s
No (60.0) 99 -
Yes (40.0) 66 -
vWF Activity normal vWF Activity decient Fischer’s
No (61.4) 97 (50.0) 7 0.288
Yes (38.6) 61 (50.0) 7
Cutaneous Symptoms
FVIII normal FVIII decient Fischer’s
No (64.0) 103 (40.0) 2 0.260
Yes (36.0) 58 (60.0) 3
FII normal FII decient Fischer’s
No (61.0) 36 (100) 2 0.384
Yes (39.0) 23 0
FV normal FV decient Fischer’s
No (64.6) 31 (64.7) 11 0.617
Yes (35.4) 17 (35.3) 6
FVII normal FVII decient Fischer’s
No (65.0) 41 - 0.586
Table 2: Relationship between bleeding questions and clotting factors
A signicant relationship was found between Factor
V deciency and two bleeding questions: GI bleed and Surgery
(Table 2). GI bleeding and F-V were signicantly related (P–val-
ue 0.028), as 6 (35.5%) out of 17 F-V decient respondents con-
rmed bleeding, compared to 5 (10.4%) out of 48 with normal
F-V value. Surgery and F-V were signicantly related (P–value
0.017), as out of 48 respondents with normal F-V value only 6
(12.5%) had bleeding during the surgery, while out of 17 F-V
decient respondents, 7 (41.2%) had bleeding during surgery.
Signicant relationship was found between bleeding
symptom responses and PT and APTT values (Table 3). Epistax-
is response, oral bleeding, and surgery were signicantly related
to PT (P–value 0.02, 0.012, and 0.039, respectively). Cutane-
ous response, bleeding from minor wounds, and menorrhagia
were signicantly related to APTT (P–value <0.0001, 0.038, and
<0.0001 respectively).
Table 4 shows the score ranges for each symptom and
its likelihood. We show the highest likelihood for a factor when a
score value is presented. For most clotting factors, the likelihood
is highest for score 1.

JScholar Publishers
J Cardio Vasc Med 2021 | Vol 7: 202
5
Yes (35.0) 22 -
FIX normal FIX decient Fischer’s
No (60.2) 80 (100) 5 0.085
Yes (39.8) 53 0
FXII normal FXII decient Fischer’s
No (73.3) 33 -
Yes (26.7) 12 -
FXIII normal FXIII decient Fischer’s
No (51.2) 21 -
Yes (48.8) 20 -
FX normal FX decient Fischer’s
No (60.0) 33 0 0.411
Yes (40.0) 22 (100) 1
vWF Ag normal vwfAg decient Fischer’s
No (64.2) 106 -
Yes (36.8) 59 -
vWF Activity normal vWF Activity decient Fischer’s
No (66.5) 105 (64.3) 9 0.541
Yes (33.5) 53 (35.7) 5
Bleeding Minor Wounds
FVIII normal FVIII decient Fischer’s
No (81.4) 131 (80.0) 4 0.65
Yes (18.6) 30 (20.0) 1
FII normal FII decient Fischer’s
No (74.6) 44 (100.0) 2 0.566
Yes (25.4) 15 0
FV normal FV decient Fischer’s
No (77.1) 37 (76.5) 13 0.6
Yes (22.9) 11 (23.5) 4
FVII normal FVII decient Fischer’s
No (77.8) 49 (50.0) 1 0.411
Yes (22.2) 14 (50.0) 1
FIX normal FIX decient Fischer’s
No (80.5) 107 (60.0) 3 0.267
Yes (19.5) 26 (40.0) 2
FXIII normal FXIII decient Fischer’s
No (75.6) 31 -
Yes (24.4) 10 -
FX normal FX decient Fischer’s
No (74.5) 41 (100) 1 0.75
Yes (25.5) 14 0
vWF Ag normal vwfAg decient Fischer’s
No (82.4) 136 -
Yes (17.6) 29 -
vWF Activity normal vWF Activity decient Fischer’s
No (81.6) 129 (92.9) 13 0.258
Yes (18.4) 29 (7.1) 1
Oral Bleeding
FVIII normal FVIII present Fischer’s
No (46.0) 74 (60.0) 3 0.432

JScholar Publishers
J Cardio Vasc Med 2021 | Vol 7: 202
6
Yes (54.0) 87 (40.0) 2
FII normal FII decient Fischer’s
No (54.2) 32 0 0.222
Yes (45.8) 27 (100.0) 2
FV normal FV decient Fischer’s
No (56.2) 27 (47.1) 8 0.579
Yes (43.8) 21 (52.9) 9 0.355
FVII normal FVII decient Fischer’s
No (54.0) 34 (50.0) 1 0.714
Yes (46.0) 29 (50.0) 1
FIX normal FIX decient Fischer’s
No (44.4) 59 (60.0) 3 0.404
Yes (55.6) 74 (40.0) 2
FXIII normal FXIII decient Fischer’s
No (48.8) 20 -
Yes (51.2) 21 -
FX normal FX decient Fischer’s
No (52.7) 29 0 0.482
Yes (47.3) 26 (100) 1
vWF Ag normal vwfAg decient Fischer’s
No (45.5) 75 -
Yes (54.5) 90 -
vWF Activity normal vWF Activity decient Fischer’s
No (45.6) 72 (50.0) 7 0.482
Yes (54.4) 86 (50.0) 7
GI Bleeding
FVIII normal FVIII decient Fischer’s
No (92.5) 149 (80.0) 4 0.338
Yes (7.5) 12 (20.0) 1
FII normal FII decient Fischer’s
No (81.4) 48 (100) 2 0.669
Yes (18.6) 11 0
FV normal FV decient Fischer’s
No (89.6) 43 (64.7) 11 0.028
Yes (10.4) 5 (35.3) 6
FVII normal FVII decient Fischer’s
No (82.5) 52 (100) 2 0.688
Yes (17.5) 11 0
FIX normal FIX decient Fischer’s
No (91.7) 122 (100.0) 5 0.656
Yes (8.3) 11 0
FXIII normal FXIII decient Fischer’s
No (85.4) 35 -
Yes (14.6) 6 -
FX normal FX decient Fischer’s
No (80.0) 44 (100) 1 0.804
Yes (20.0) 11 (0) 0
vWF Ag normal vwfAg decient Fischer’s
No (92.7) 153 -

JScholar Publishers
J Cardio Vasc Med 2021 | Vol 7: 202
7
Yes (7.3) 12 -
vWF Activity normal vWF Activity decient Fischer’s
No (93.0) 147 (92.86) 13
Yes (7.0) 11 (7.1) 1
Surgery
FVIII normal FVIII decient Fischer’s
No (83.8) 135 (100) 5 0.422
Yes (16.2) 26 0
FII normal FII decient Fischer’s
No (79.7) 47 (50) 1 0.384
Yes (20.3) 12 (50) 1
FV normal FV decient Fischer’s
No (87.5) 42 (58.8) 10 0.017
Yes (12.5) 6 (41.2) 7
FVII normal FVII decient Fischer’s
No (80.9) 51 (50.0) 1 0.363
Yes (19.1) 12 (50.0) 1
FIX normal FIX decient Fischer’s
No (83.5) 111 (60.0) 3 0.208
Yes (16.5) 22 (40.0) 2
FXIII normal FXIII decient Fischer’s
No (82.9) 34 -
Yes (17.1) 7 -
FX normal FX decient Fischer’s
No (80.0) 44 (100) 1 0.804
Yes (20.0) 11 (0) 0
vWF Ag normal vwfAg decient Fischer’s
No (83.6) 138 -
Yes (16.4) 27 -
vWF Activity normal vWF Activity decient Fischer’s
No (84.2) 133 (85.7) 12 0.619
Yes (15.8) 25 (14.3) 2
Muscle /hemarthrosis
FVIII normal FVIII decient Fischer’s
No (96.3) 155 (100) 5 0.83
Yes (3.7) 6 0
FII normal FII decient Fischer’s
No (96.6) 57 (3.4) 2 0.935
Yes (3.4) 2 0
FV normal FV decient Fischer’s
No (97.9) 47 (94.1) 16 0.458
Yes (2.1) 1 (5.9) 1
FVII normal FVII decient Fischer’s
No (96.8) 61 (100) 2
Yes (3.2) 2 0
FIX normal FIX decient Fischer’s
No (95.5) 127 (100.0) 5 0.798
Yes (4.5) 6 0
FXIII normal FXIII decient Fischer’s
No (95.1) 39 -
Yes (4.9) 2 -
FX normal FX decient Fischer’s

JScholar Publishers
J Cardio Vasc Med 2021 | Vol 7: 202
8
No (96.4) 53 (100) 1 0.964
Yes (3.6) 2 (0) 0
vWFAg normal vwfAg decient Fischer’s
No (96.4) 159 -
Yes (3.6) 6 -
Vwf Activity normal Vwf Activity decient Fischer’s
No (96.2) 152 (100.0) 14 0.596
Yes (3.8) 6 0
Menorrhagia
FVIII normal FVIII decient Fischer’s
No (75.3) 76 (75.0) 3 0.686
Yes (24.7) 25 (25.0) 1
FII normal FII decient Fischer’s
No (63.2) 24 0 0.385
Yes (36.8) 14 (100) 1
FV normal FV decient Fischer’s
No (60.6) 20 (71.4) 5 0.467
Yes (39.4) 13 (28.6) 2
FVII normal FVII decient Fischer’s
No (64.1) 25 0 0.375
Yes (35.9) 14 (100) 1
FIX normal FIX decient Fischer’s
No (73.6) 67 (100) 2 0.548
Yes (26.4) 24 0
FXIII normal FXIII decient Fischer’s
No (71.9) 23 -
Yes (28.1) 9 -
FX normal FX decient Fischer’s
No (61.1) 22 (100) 1 0.622
Yes (38.9) 14 (0) 0
vWFAg normal vwfAg decient Fischer’s
No (74.5) 76 -
Yes (25.5) 26 -
Vwf Activity normal Vwf Activity decient Fischer’s
No (74.7) 74 (80.0) 4 0.633
Yes (25.3) 25 (20.0) 1
Epistaxis
PT normal PT prolonged Fischer’s
No (56.6) 232 (65.2) 150 0.020
Yes (43.4) 178 (34.8) 80
APT normal APT prolonged Fischer’s
No (58.0) 134 (60.8) 247 0.269
Yes (42.0) 97 (39.2) 159
Cutaneous symptoms
PT normal PT prolonged Fischer’s
No (71.5) 293 (74.4) 171 0.245
Yes (28.5) 117 (25.6) 59
APT normal APT prolonged Fischer’s
Table 3: Relationship between bleeding questions and, PT Pat and APT Pat using Fisher exact test

JScholar Publishers
J Cardio Vasc Med 2021 | Vol 7: 202
9
No (62.3) 144 (78.3) 318 0.0001>
Yes (37.7) 87 (21.7) 88
Bleeding minor wounds
PT normal PT prolonged Fischer’s
No (80.5) 330 (78.3) 180 0.283
Yes (19.5) 80 (21.7) 50
APT normal APT prolonged Fischer’s
No (75.8) 175 (82.0) 333 0.038
Yes (24.2) 15 (18.0) 73
Oral Bleeding
PT normal PT prolonged Fischer’s
No (40.5) 166 (50.0) 115 0.012
Yes (59.5) 244 (50.0) 115
APT normal APT prolonged Fischer’s
No (45.0) 104 (42.8) 174 0.327
Yes (55.0) 127 (57.2) 232
GI bleeding
PT normal PT prolonged Fischer’s
No (91.9) 377 (89.1) 205 0.147
Yes (8.1) 33 (10.9) 25
APT normal APT prolonged Fischer’s
No (89.2) 206 (91.9) 373 0.160
Yes (10.8) 25 (8.1) 33
Surgery
PT Pat normal PT prolonged Fischer’s
No (83.4) 342 (77.4) 178 0.039
Yes (16.6) 68 (22.6) 52
APT Pat normal APT prolonged Fischer’s
No (83.1) 192 (80.1) 325 0.199
Yes (16.9) 39 (19.9) 81
Muscle /hemarthrosis
PT normal PT prolonged Fischer’s
No (96.6) 396 (97.0) 223 0.5
Yes (3.4) 14 (3.0) 7
APT normal APT prolonged Fischer’s
No (96.6) 223 (97.0) 394 0.446
Yes (3.4) 8 (3.0) 12
Menorrhagia
PT normal PT prolonged Fischer’s
No (86.3) 354 (87.4) 201 0.403
Yes (13.6) 56 (12.6) 29
APT normal APT prolonged Fischer’s
No (63.2) 185 (90.4) 367 0.0001 >
Yes (36.8) 46 (9.6) 39

JScholar Publishers
J Cardio Vasc Med 2021 | Vol 7: 202
10
Figure 1 shows odds ratios of Factor V to symptoms,
with GI bleeding and surgery having an odds ratio values great-
er than 5. Figure 2 shows odds ratios of Von Willebrand factor
activity as <2 for epistaxis and cutaneous symptoms, which does
not reach the threshold of signicance in predicting bleeding.
Table 4: Likelihood of Bleeding for Coagulation Factors decient using BAT scoring system
Factors Score range Likelihood
)FVIII )n=15 0-9 Score 0 likelihood 0.42
)FIX )5 0-5 Score 1 likelihood 0.60
)FXI )0 N/A N/A
)FXIII )0 N/A N/A
)vWFAg )11 1 N/A
)vWF-activity )14 0-5 Score 1 likelihood 0.57
)FII )2 1 N/A
)FV )17 1-5 Score 1 likelihood 0.5
)FVII )2 5 N/A
)FX )1 N/A N/A
Figure 3 shows the bleed score and Factor V with ROC
AUC 0.6 for Surgery, showing the predictability for surgical bleed-
ing. For a sensitivity of 0.5, the specicity is 0.8. Figure 4 shows
Factor V and PT prolongation with ROC AUC 0.67 and 0.5 for
GI bleeding, respectively, again showing Factor V deciency as a
predictor of GI bleed. For a sensitivity of 0.55, the specify is 0.8.
Figure 1: Odds-ratio for F-V compared to bleeding responses

JScholar Publishers
J Cardio Vasc Med 2021 | Vol 7: 202
11
Figure 2: Odds ratio of vWF Activity against bleeding responses
Figure 3: ROC of Surgery response to Factor-V and Bleed Score (binary variables)

JScholar Publishers
J Cardio Vasc Med 2021 | Vol 7: 202
12
Discussion
Rare bleeding disorders (RBDs) are caused by mainly
autosomal recessive inherited clotting factor deciencies of Fac-
tors I (brinogen), II (prothrombin), V, VII, X, XI, and XIII, as
well as combined FV + FVIII. Coagulation factor deciencies
comprise of congenital bleeding disorders with a heterogeneous
phenotype. ese deciencies can lead to sudden and chronic
bleeding diathesis, which poses a signicant impact on quality of
life and can be lethal in rare instances. Quantication of bleeding
disorders based upon the symptom is itself a challenging task.
We utilized a condensed MCMDM-1vWD bleeding question-
naire for ecient screening of bleeding symptoms. e bleeding
questions were related to epistaxis, cutaneous symptoms, bleed-
ing from minor wounds, oral, gastrointestinal, surgery, muscle/
hemarthrosis, and menorrhagia. To build the correlation insight,
we tested blood samples for F II, V, VII, VIII, IX, X, XI, and XIII.
A signicant correlation was found between gastrointestinal
bleeding and Factor V deciency (P-value 0.019, Fisher exact
0.028); and surgery-related questions and factor V deciency
(P-value 0.011, Fisher exact 0.017).
Figure 4: ROC of GI bleed response to F-V and PT value
Coagulation factor V is a glycoprotein that participates
in the formation of the prothrombinase complexes, a critical step
for clot formation (11). Incidence of Factor V deciency (Owren’s
disease or parahemophilia) is 1 /1,000,000 and is considered a
rare bleeding disorder in the general population (12). Although
the life-threatening manifestation is rare with factor V deciency,
however, it is manifested in a plethora of bleeding events including
mucosal bleeding as the most common manifestation.
Peyvandi, et al. in reporting the results from the Europe-
an Network of Rare Bleeding Disorders described that on linear
regression analysis, there was a strong association between clot-
ting factor activity level and clinical bleeding severity for brino-
gen, F-X, XIII, and combined V and VIII deciencies. A weaker
association was present for V and VII deciencies [16,17]. ese
factor deciencies also have been previously reported in the
Saudi population in various regions. Ahmed MA, et al. reported
FVII and X deciency in Eastern Province [13] while Al-Sharief,
et al. reported FXIII deciency in Riyadh [14]. Al-Fawaz, et al.
reported FXI, V, and VII deciency [15] and Madkhali, et al. re-
ported F-II, V, VII, X, XI, and XIII deciencies [16]. rough a
hematological panel assay, Al Numair, et al. was able to identify
eleven FV deciency patients with mutations [17].

JScholar Publishers
J Cardio Vasc Med 2021 | Vol 7: 202
13
A total of 321 cases of rare clotting factor deciency
were reported by Shetty, et al. from India, with 30% of patients
having FXIII deciency, 15.6% of patients with FX, 15% cases
with FVII deciency, 12.1% with brinogen deciency, 9% with
FXI deciency, 5.6% with combined V and VIII deciency, and
2.1% with congenital multiple vitamin K‐dependent coagulation
factor deciency [18].
Epistaxis is oen presented as a common emergency,
and routine coagulation studies such as PT and APTT have been
questioned as a reliable marker for diagnosis [19]. e current
study suggests the notion that prolonged PT and APTT in the
presence of bleeding symptoms could be used as screening tests
to predict underlying factor deciency. Yet the absence of ab-
normal PT APTT doesn’t rule out clotting factor deciency. In
contrast to our study, Elden, et al. reported a limited value of PT
and APTT in predicting bleeding disorders in children, arguing
that PT, APTT only identify 20% of cases with bleeding disor-
ders [20], while Al Zahrani, et al. demonstrated limited predict-
ability power of routine coagulation testing in pediatric patients
undergoing surgery [21]. Such discrepancies signify the ethnic
distribution of hereditary elements and indicate the importance
of regional studies. e rationale of the current study lies in the
fact that specic bleeding symptoms may correlate with underly-
ing genetic defects such as coagulation factor deciency. A signif-
icant relationship between certain bleeding symptoms (GI and
Surgery) with factor V deciency warrant that such association
must be studied nationwide to establish a bleeding questionnaire
as a diagnostic tool.
Conclusion
Identication of clotting factor deciency can signi-
cantly improve clinical management with better patient out-
comes. e current study is an epidemiological survey which
aimed to explore the correlation of bleeding symptoms with
clotting factor deciency, and a signicant correlation was found
between factor V deciency and bleeding from GI and surgery
independently. ese correlations demand further studies with
greater sample size to increase the power of such associations
and establish validated methods to predict factor deciencies
resulting in improved management for patients with bleeding
symptoms.
Declarations
Authors’ Contribution
KS & TO designed & developed the study. Both authors
were responsible for contents & authenticity. NAN, AS, MZ, AA
oversaw data collection, data entry. NAO, EA, NB, AT carried
out nal review of data and analysis. FZ, FA, AAA were responsi-
ble for direction of the study team, and facilitation of the project
plan.
Funding and Source of Support
KACST (408-34)
Ethics approval and consent to participate
e study was approved by the Institutional Review
Board of King Faisal Specialist Hospital and Research Cen-
ter, Kingdom of Saudi Arabia, with approval # RAC KFSHRC
(2130036).
Consent for publication
All authors consent for publication.
Availability of data and materials
Furnished upon request.
Competing interests
None declared.

JScholar Publishers
J Cardio Vasc Med 2021 | Vol 7: 202
14
References
1. Castaman G, Linari S (2017) Diagnosis and treatment
of von Willebrand disease and rare bleeding disorders. J clin med
6: 45.
2. Rhynders PA, Sayers CA, Presley RJ, ierry JM (2014)
Providing young women with credible health information about
bleeding disorders. Ame J preventive med 47: 674-80.
3. James P, Salomon O, Mikovic D, Peyvandi F (2014) Rare
bleeding disorders–bleeding assessment tools, laboratory aspects
and phenotype and therapy of FXI deciency. Haemophilia 20:
71-5.
4. Boender J, Kruip M, Leebeek F (2016) A diagnostic ap-
proach to mild bleeding disorders. J rombosis Haemostasis
14: 1507-16.
5. Bowman M, Mundell G, Grabell J, Hopman W, Rapson
D, et al. (2008) Generation and validation of the Condensed MC-
MDM‐1VWD Bleeding Questionnaire for von Willebrand dis-
ease. J thrombosis haemostasis 6: 2062-6.
6. Moenen F, Nelemans P, Schols S, Schouten H, Henskens
Y, et al. (2018) e diagnostic accuracy of bleeding assessment
tools for the identication of patients with mild bleeding disor-
ders: a systematic review. Haemophilia 24: 525-35.
7. Peyvandi F, Di Michele D, Bolton-Maggs P, Lee C, Tri-
podi A, et al. (2012) Classication of rare bleeding disorders
(RBDs) based on the association between coagulant factor activ-
ity and clinical bleeding severity. J thrombosis haemostasis: JTH
10: 1938.
8. Chandler E, Kakkar N, Kaur R (2019) Comparison of
Rapid Centrifugation Technique with Conventional Centrifuga-
tion for Prothrombin Time (PT) and Activated Partial rombo-
plastin Time (APTT) Testing. Ind J of Hematology Blood Trans-
fusion 35: 161-6.
9. Tosetto A, Rodeghiero F, Castaman G, Goodeve A, Fed-
erici A, et al. (2006) A quantitative analysis of bleeding symp-
toms in type 1 von Willebrand disease: results from a multicenter
European study (MCMDM‐1 VWD). J rombosis Haemostasis
4: 766-73.
10. Rydz N, James PD (2012) e evolution and value of
bleeding assessment tools. J rombosis Haemostasis 10: 2223-9.
11. Kane WH, Majerus PW (1981) Purication and char-
acterization of human coagulation factor V. J Biolog Chem 256:
1002-7.
12. Tabibian S, Shiravand Y, Shams M, Safa M, Gholami
MS, et al. (2019) editors. A comprehensive overview of coagu-
lation factor V and congenital factor V deciency. Seminars in
thrombosis and hemostasis; 2019: ieme Medical Publishers.
13. Ahmed MA, Al-Sohaibani M, Al-Mohaya S, Sumer T,
Al-Sheikh E, et al. (1988) Inherited bleeding disorders in the
Eastern Province of Saudi Arabia. Acta haematologica 79: 202-6.
14. Al-Sharif FZ, Aljurf MD, Al-Momen AM, Ajlan AM,
Musa MO, et al. (2002) Clinical and laboratory features of con-
genital factor XIII deciency. Saudi Med J 23: 552-4.
15. Al-Fawaz IM, Gader AM, Bahakim HM, Al-Mohareb
F, Al-Momen AK, et al. (1996) Hereditary bleeding disorders in
Riyadh, Saudi Arabia. Annals Saudi med16: 257-61.
16. Madkhali I, Owaidah T, Riash MA, Naser R, Al-Zah-
rani H (2012) Rare inherited clotting factor deciencies: A sin-
gle-center experience. Journal of Applied Hematology 3: 36.
17. Al-Numair NS, Ramzan K, Saleh M, Alzahrani H, Tar-
awah A, et al. (2019) First description of the molecular and clin-
ical characterization of hereditary factor V deciency in Saudi
Arabia: report of four novel mutations. Blood Coagulation &
Fibrinolysis 30: 224-32.
18. Shetty S, Shelar T, Mirgal D, Nawadkar V, Pinto P, et
al. (2014) Rare coagulation factor deciencies: a countrywide
screening data from India. Haemophilia 20: 575-81.
19. Awan MS, Iqbal M, Imam SZ (2008) Epistaxis: when are
coagulation studies justied? Emergency Med J 25: 156-7.
20. Elden L, Reinders M, Witmer C (2012) Predictors of
bleeding disorders in children with epistaxis: value of preoper-
ative tests and clinical screening. Int J ped otorhinolaryngology
76: 767-71.
21. Alzahrani A, Othman N, Bin-Ali T, Elfaraidi H, Al
Mussaed E, et al. (2019) Routine preoperative coagulation tests
in children undergoing elective surgery or invasive procedures:
are they still necessary? Clinical Medicine Insights: Blood Disor-
ders 12: 1179545X18821158.

JScholar Publishers
J Cardio Vasc Med 2021 | Vol 7: 202
15
Submit your manuscript at
http://www.jscholaronline.org/submit-manuscript.php
Submit your manuscript to a JScholar journal
and benefit from:
¶Convenient online submission
¶Rigorous peer review
¶Immediate publication on acceptance
¶Open access: articles freely available online
¶High visibility within the field
¶Better discount for your subsequent articles