Hereditary combined deficiency of vitamin K-dependent clotting factors

What it is

From: Orphanet

Combined vitamin K-dependent clotting factors deficiency (VKCFD) is a congenital bleeding disorder resulting from variably decreased levels of coagulation factors II, VII, IX and X, as well as natural anticoagulants protein C, protein S and protein Z.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abnormal bleeding · Frequent (79-30%)

An abnormal susceptibility to bleeding, often referred to as a bleeding diathesis. A bleeding diathesis may be related to vascular, platelet and coagulation defects.

Bruising susceptibility · Frequent (79-30%)

An ecchymosis (bruise) refers to the skin discoloration caused by the escape of blood into the tissues from ruptured blood vessels. This term refers to an abnormally increased susceptibility to bruising. The corresponding phenotypic abnormality is generally elicited on medical history as a report of frequent ecchymoses or bruising without adequate trauma.

Decreased level of heparin co-factor II · Frequent (79-30%)

An abnormality of coagulation related to a decreased concentration of heparin co-factor II

Prolonged partial thromboplastin time · Frequent (79-30%)

Increased time to coagulation in the partial thromboplastin time (PTT) test, a measure of the intrinsic and common coagulation pathways. Phospholipid, and activator, and calcium are mixed into an anticoagulated plasma sample, and the time is measured until a thrombus forms.

Prolonged prothrombin time · Frequent (79-30%)

Increased time to coagulation in the prothrombin time test, which is a measure of the extrinsic pathway of coagulation. The results of the prothrombin time test are often expressed in terms of the International normalized ratio (INR), which is calculated as a ratio of the patient's prothrombin time (PT) to a control PT standardized for the potency of the thromboplastin reagent developed by the World Health Organization (WHO) using the formula: INR is equal to Patient PT divided by Control PT.

Reduced factor IX activity · Frequent (79-30%)

Decreased activity of coagulation factor IX. Factor IX, which itself is activated by factor Xa or factor VIIa to form factor IXa, activates factor X into factor Xa.

Reduced factor VII activity · Frequent (79-30%)

Reduced activity of coagulation factor VII. Factor VII is part of the extrinsic coagulation pathway, which is initiated at the site of injury in response to the release of tissue factor (fIII). Tissue factor and activated factor VII catalyze the activation of factor X.

Reduced factor X activity · Frequent (79-30%)

Reduced activity of coagulation factor X. The extrinsic and intrinsic pathways converge at factor X (fX). The extrinsic pathway activates fX by means of d factor VII with its cofactor, tissue factor. The intrinsic pathway activates fX by means of the tenase complex (Ca2+ and factors VIIIa, IXa and X) on the surface of activated platelets. Factor Xa in turn activates prothrombin (factor II) to thrombin (factor IIa).

Reduced protein C activity · Frequent (79-30%)

An abnormality of coagulation related to a decreased concentration of vitamin K-dependent protein C. Protein C is activated to protein Ca by thrombin bound to thrombomodulin. Activated protein C degrades factors VIIIa and Va.

Reduced protein S activity · Frequent (79-30%)

An abnormality of coagulation related to a decreased concentration of vitamin K-dependent protein S. Protein S is a cofactor of protein C.

Angioid streaks of the fundus · Occasional (29-5%)

Irregular lines in the outer retina and Bruch membrane that are typically configured in a radiating fashion and emanate from the optic disc. Angioid streaks are crack-like dehiscences in abnormally thickened and calcified Bruch membrane, resulting in atrophy of the overlying retinal pigment epithelium. They may be associated with a number of endocrine, metabolic, and connective tissue abnormalities but can be idiopathic. They can be associated with neovascular complexes (choroid).

Atherosclerosis · Occasional (29-5%)

A condition characterized by patchy atheromas or atherosclerotic plaques which develop in the walls of medium-sized and large arteries and can lead to arterial stenosis with reduced or blocked blood flow.

Cephalohematoma · Occasional (29-5%)

Hemorrhage between the skull and periosteum of a newborn resulting from rupture of blood vessels that cross the periosteum.

Cutis laxa · Occasional (29-5%)

Wrinkled, redundant, inelastic and sagging skin.

Other findings in the same source

From: Orphanet

Additional reported features include Ecchymosis (Occasional (29-5%)); Epiphyseal stippling (Occasional (29-5%)); Epistaxis (Occasional (29-5%)); Hypoplasia of the nasal bone (Occasional (29-5%)); Intracranial hemorrhage (Occasional (29-5%)); Joint hemorrhage (Occasional (29-5%)); Menorrhagia (Occasional (29-5%)); Osteoporosis (Occasional (29-5%)); Post-partum hemorrhage (Occasional (29-5%)); Prolonged bleeding following circumcision (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: Orphanet

Adolescent; Adult; Infancy; Neonatal

Inheritance in the source

From: Orphanet

Autosomal recessive

Frequency and the population described

From: Orphanet

Reported case(s): 272.0; Worldwide. This is a published case count, not prevalence. Point prevalence: <1 / 1 000 000; Worldwide; Class only.

Understanding the inheritance label

From: MedlinePlus Genetics

An autosomal recessive pattern usually involves disease-causing changes in both copies of a gene. Parents may each carry one altered copy without having the condition themselves. A genetic counsellor can explain carrier testing and reproductive implications using the actual laboratory findings, rather than the condition name alone.

Which doctor should you see?

The suggested department for discussing Hereditary combined deficiency of vitamin K-dependent clotting factors is Haematology, with a haematologist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Which blood-cell, marrow, bleeding or clotting finding matters most?
• Does the diagnosis need confirmation or a more precise subtype?
• Which symptoms or laboratory changes should trigger earlier review?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Hereditary combined deficiency of vitamin K-dependent clotting factors. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.